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<input type="email" aria-label="Sender Email Address" placeholder="email@example.com" id="email-from" class="email-from" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="256">
</div>
<div class="action-panel-control-wrap">
<label for="email-citation-format" class="action-panel-label">
Format:
</label>
<select id="email-citation-format" name="citation-format" class="action-panel-selector email-citation-format">
<option selected="selected" value="summary">Summary</option>
<option value="summary-text">Summary (text)</option>
<option value="abstract">Abstract</option>
<option value="abstract-text">Abstract (text)</option>
</select>
</div>
<div class="include-supplemental-container">
<input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental">
<label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label>
</div>
<div class="form-field recaptcha ">
<div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div>
</div>
<div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="send">
Send email
</button>
<button class="action-panel-cancel"
aria-label="Close 'Email citations' panel"
ref="linksrc=close_email_panel"
aria-controls="email-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="cancel">
Cancel
</button>
</div>
<input type="hidden" name="email-search-details" value="" />
<input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" />
</form>
</div>
</div>
<div id="collections-action-panel"
class="collections-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-collections-open-panel-enabled="false"
data-collections-open-panel-url-hash="#open-collections-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to Collections
</h3>
<form id="collections-action-panel-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-myncbi-max-collection-name-length="100"
data-add-to-collection-max-amount="1000"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/">
<input type="hidden" name="csrfmiddlewaretoken" value="ygHiGeOcXQcgUiFaqga2um2kbng8kNlwP3rnj4hyxrZKOJL03zN4YuyYJrYkdoTQ">
<div class="choice-group" role="radiogroup">
<ul class="radio-group-items">
<li>
<input type="radio"
id="collections-action-panel-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_new">
<label for="collections-action-panel-new">Create a new collection</label>
</li>
<li>
<input type="radio"
id="collections-action-panel-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_existing">
<label for="collections-action-panel-existing">Add to an existing collection</label>
</li>
</ul>
</div>
<div class="controls-wrapper">
<div class="action-panel-control-wrap new-collections-controls">
<label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label>
<input
type="text"
name="add-to-new-collection"
id="collections-action-panel-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
data-ga-category="save_share"
data-ga-action="create_collection"
data-ga-label="non_favorties_collection">
<div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
Name must be less than 100 characters
</div>
</div>
<div class="action-panel-control-wrap existing-collections-controls">
<label for="collections-action-panel-add-to-existing" class="action-panel-label">
Choose a collection:
</label>
<select id="collections-action-panel-add-to-existing"
class="action-panel-selector collections-action-add-to-existing"
data-ga-category="save_share"
data-ga-action="select_collection"
data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'">
</select>
<div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your collection due to an error<br>
<a href="#">Please try again</a>
</div>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="add">
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to Collections' panel"
ref="linksrc=close_collections_panel"
aria-controls="collections-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="bibliography-action-panel"
class="bibliography-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-bibliography-open-panel-enabled="false"
data-bibliography-open-panel-url-hash="#open-bibliography-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to My Bibliography
</h3>
<form id="bibliography-action-panel-form"
class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-add-to-bibliography-max-amount="100"
data-add-to-bibliography-batch-size="10"
data-bibliography-delegates-url="/list-bibliography-delegates/"
data-add-to-bibliography-url="/add-to-bibliography/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/">
<input type="hidden" name="csrfmiddlewaretoken" value="ygHiGeOcXQcgUiFaqga2um2kbng8kNlwP3rnj4hyxrZKOJL03zN4YuyYJrYkdoTQ">
<div class="action-panel-control-wrap bibliographies-controls">
<div class="choice-group">
<ul class="bibliographies-action-add radio-group-items">
<li>
<input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/>
<label for="my-bibliography">My Bibliography</label>
</li>
</ul>
</div>
</div>
<div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your delegates due to an error<br>
<a href="#">Please try again</a>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore>
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to bibliography' panel"
ref="linksrc=close_bibliography_panel"
aria-controls="bibliography-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="mybib"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true"
data-saved-search-open-panel-enabled="false"
data-saved-search-open-panel-url-hash="#open-saved-search-panel">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your saved search
</h2>
<form id="saved-search-action-panel-form"
class="saved-search-action-panel-form action-panel-content action-form"
data-create-saved-search-url="/create-saved-search/"
data-try-search-terms-url="/try-search-term/"
data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/">
<input type="hidden" name="csrfmiddlewaretoken" value="ygHiGeOcXQcgUiFaqga2um2kbng8kNlwP3rnj4hyxrZKOJL03zN4YuyYJrYkdoTQ">
<div class="action-panel-control-wrap">
<label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk">
Name of saved search:
</label>
<input maxlength="200"
type="text"
name="saved-search-name"
id="saved-search-name"
class="saved-search-name"
value=""
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-term" class="action-panel-label required-field-asterisk">
Search terms:
</label>
<textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea>
</div>
<div class="test-search-term-wrap">
<a href="#" class="try-search-term">Test search terms</a>
</div>
<div class="choice-group action-panel-extra-margin-top">
<span class="action-panel-label" id="fieldset-label">
Would you like email updates of new search results?
</span>
<fieldset id="saved-search-alert" aria-describedby="fieldset-label">
<legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend>
<ul class="radio-group-items">
<li>
<input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked>
<label for="saved-search-alert-yes" class="action-panel-label">Yes</label>
</li>
<li>
<input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no">
<label for="saved-search-alert-no" class="action-panel-label">No</label>
</li>
</ul>
</fieldset>
</div>
<div class="alert-schedule-wrap">
<div class="action-panel-control-wrap">
<label class="action-panel-label">
Email:
</label>
<span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span>
</div>
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="saved-search-frequency" class="action-panel-label">
Frequency:
</label>
<select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency">
<option value="monthly">Monthly</option>
<option value="weekly">Weekly</option>
<option value="daily">Daily</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-monthly-additional">
<label for="saved-search-monthly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-monthly-on-day" class="no-border-panel-selector">
<option value="Sunday">The first Sunday</option>
<option value="Monday">The first Monday</option>
<option value="Tuesday">The first Tuesday</option>
<option value="Wednesday">The first Wednesday</option>
<option value="Thursday">The first Thursday</option>
<option value="Friday">The first Friday</option>
<option value="Saturday">The first Saturday</option>
<option value="day">The first day</option>
<option value="weekday">The first weekday</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-weekly-additional">
<label for="saved-search-weekly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day">
<option value="Sunday">Sunday</option>
<option value="Monday">Monday</option>
<option value="Tuesday">Tuesday</option>
<option value="Wednesday">Wednesday</option>
<option value="Thursday">Thursday</option>
<option value="Friday">Friday</option>
<option value="Saturday">Saturday</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-report" class="action-panel-label">
Report format:
</label>
<select id="saved-search-report" class="no-border-panel-selector saved-search-report">
<option value="DocSum">Summary</option>
<option value="DocSumText">Summary (text)</option>
<option value="Abstract">Abstract</option>
<option value="AbstractText">Abstract (text)</option>
<option value="MEDLINE">PubMed</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-amount" class="action-panel-label">
Send at most:
</label>
<select id="saved-search-amount" class="no-border-panel-selector saved-search-amount">
<option value="1">1 item</option>
<option value="5" selected>5 items</option>
<option value="10">10 items</option>
<option value="20">20 items</option>
<option value="50">50 items</option>
<option value="100">100 items</option>
<option value="200">200 items</option>
</select>
</div>
<div>
<input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result">
<label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox">
Send even when there aren't any new results
</label>
</div>
<div class="action-panel-control-wrap option-text-in-email-wrap">
<label for="saved-search-email-text" class="action-panel-label">
Optional text in email:
</label>
<textarea name="saved-search-email-text"
id="saved-search-email-text"
class="saved-search-email-text"></textarea>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Saving..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Save
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your saved search' panel"
ref="linksrc=close_saved_search_panel"
aria-controls="saved-search-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Create a file for external citation management software
</h2>
<form id="citation-manager-action-panel-form"
class="action-panel-content action-form"
action="/results-export-ids/"
data-by-search-action="/results-export-search-data/"
data-by-ids-action="/results-export-ids/"
method="post"
data-by-search-method="post"
data-by-ids-method="post">
<input type="hidden" name="csrfmiddlewaretoken" value="ygHiGeOcXQcgUiFaqga2um2kbng8kNlwP3rnj4hyxrZKOJL03zN4YuyYJrYkdoTQ">
<input name="results-format" type="hidden" value="pubmed"/>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="save">
Create file
</button>
<button class="action-panel-cancel"
aria-label="Close 'Send citations to citation manager' panel"
ref="linksrc=close_citation_manager_panel"
aria-controls="citation-manager-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your RSS Feed
</h2>
<form id="rss-action-panel-form"
class="rss-action-panel-form action-panel-content action-form"
data-create-rss-feed-url="/create-rss-feed-url/"
data-search-form-term-value="">
<input type="hidden" name="csrfmiddlewaretoken" value="ygHiGeOcXQcgUiFaqga2um2kbng8kNlwP3rnj4hyxrZKOJL03zN4YuyYJrYkdoTQ">
<div class="action-panel-control-wrap">
<label for="rss-name" class="action-panel-label required-field-asterisk">
Name of RSS Feed:
</label>
<input maxlength="200"
placeholder="Name"
type="text"
name="rss-name"
id="rss-name"
class="rss-name"
value=''
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="rss-limit-wrap">
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="rss-limit" class="action-panel-label">
Number of items displayed:
</label>
<select id="rss-limit" class="no-border-panel-selector rss-limit">
<option value="5">5</option>
<option value="10">10</option>
<option value="15" selected="selected">15</option>
<option value="20">20</option>
<option value="50">50</option>
<option value="100">100</option>
</select>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Creating..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Create RSS
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your RSS' panel"
ref="linksrc=close_rss_panel"
aria-controls="rss-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
<div class="action-panel-control-wrap rss-link-copy-wrap">
<label for="rss-link" class="usa-sr-only">RSS Link</label>
<input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link">
<button
type="button"
disabled
class="rss-link-copy-button disabled"
data-ga-category="save_share"
data-ga-action="rss"
data-ga-label="copy">
Copy
</button>
</div>
</form>
</div>
</div>
</div>
</div>
<div class="article-page" id="article-page" data-article-pmid="12917324">
<aside class="page-sidebar">
<div class="inner-wrap">
<div class="full-text-links">
<div class="full-view">
<h3 class="title">
Full text links
</h3>
<div class="full-text-links-list">
<a class="link-item
dialog-focus"
href="https://www.tandfonline.com/doi/10.1128/MCB.23.17.5989-5999.2003?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub 0pubmed"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=False&amp;PrId=4487&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=12917324&amp;db=pubmed&amp;nlmid=8109087"
title="See full text options at Atypon"
data-ga-category="full_text"
data-ga-action="Atypon"
data-ga-label="12917324"
><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--www.tandfonline.com-pb-assets-tandf-logos-tf_pubmed_fulltext_icon.png" alt="Atypon full text link"><span class="text">
Atypon
</span></a><a class="link-item
pmc
"
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/12917324/"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=True&amp;PrId=3494&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=12917324&amp;db=pubmed&amp;nlmid=8109087"
title="Free full text at PubMed Central"
data-ga-category="full_text"
data-ga-action="PMC"
data-ga-label="12917324"
><span class="text">
Free PMC article
</span></a>
</div>
</div>
<div class="short-view">
<a href="#" class="full-text-links-button full-text-links-dialog-trigger">
Full text links
</a>
</div>
</div>
<div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger"
aria-label="Open dialog with citation text in different styles"
data-ga-category="save_share"
data-ga-action="cite"
data-ga-label="open"
data-all-citations-url="/12917324/citations/"
data-citation-style="nlm"
data-pubmed-format-link="/12917324/export/"><span class="button-label">Cite</span></button><link type="text/css" href="ncbi-overlay-block/src/overlay-block.css"><div class="collections-button-container" data-article-id="12917324" data-article-db="pubmed"><button class="collections-button collections-dialog-trigger"
aria-label="Save article in MyNCBI collections."
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_button"
data-collections-open-dialog-enabled="false"
data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F12917324%2F%23open-collections-dialog"
data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog"
class="dialog collections-dialog"
aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-myncbi-max-collection-name-length="100"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="ygHiGeOcXQcgUiFaqga2um2kbng8kNlwP3rnj4hyxrZKOJL03zN4YuyYJrYkdoTQ"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio"
id="collections-action-dialog-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio"
id="collections-action-dialog-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label><input
type="text"
name="add-to-new-collection"
id="collections-action-dialog-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
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Functional dissection of eyes absent reveals new modes of regulation within the retinal determination gene network
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The retinal determination (RD) gene network encodes a group of transcription factors and cofactors necessary for eye development. Transcriptional and posttranslational regulation of RD family members is achieved through interactions within the network and with extracellular signaling pathways, including epidermal growth factor receptor/RAS/mitogen-activated protein kinase (MAPK), transforming growth factor beta/DPP, Wingless, Hedgehog, and Notch. Here we present the results of structure-function analyses that reveal novel aspects of Eyes absent (EYA) function and regulation. We find that the conserved C-terminal EYA domain negatively regulates EYA transactivation potential, and that GROUCHO-SINE OCULIS (SO) interactions provide another mechanism for negative regulation of EYA-SO target genes. We have mapped the transactivation potential of EYA to an internal proline-, serine-, and threonine-rich region that includes the EYA domain 2 (ED2) and two MAPK phosphorylation consensus sites and demonstrate that activation of the RAS/MAPK pathway potentiates transcriptional output of EYA and the EYA-SO complex in certain contexts. Drosophila S2 cell two-hybrid assays were used to describe a novel homotypic interaction that is mediated by EYA's N terminus. Our data suggest that EYA requires homo- and heterotypic interactions and RAS/MAPK signaling responsiveness to ensure context-appropriate RD gene network activity.
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itemscope itemtype="http://schema.org/ImageObject"
itemprop="associatedMedia"
data-slide-index="0"
data-label-slug="fig-1">
<a class="figure-link"
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec45/180989/b076f15cab81/mb1731947001.jpg"
itemprop="contentUrl"
aria-describedby="figure-caption-0"
role="button"
data-image-width="623"
data-image-height="370"
data-image-alt="FIG. 1."
data-pmc-id="PMC180989"
data-figure-id="f1">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-0"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec45/180989/9961f03560cb/mb1731947001.gif"
alt="FIG. 1." />
</a>
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="623">
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="370">
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
<div class="caption-wrap">
<strong class="figure-label">
<p> FIG. 1. </p>
</strong>
<div class="figure-caption-contents"><p> The N-terminus of EYA is… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> FIG. 1. </p>
</strong>
<div class="figure-caption-contents"><p> The N-terminus of EYA is a potent transactivator. (A) <i> Drosophila </i> EYA contains two… </p></div>
</div>
<figcaption id="figure-caption-0" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
FIG. 1.
</strong>
<div class="figure-caption-contents">The N-terminus of EYA is a potent transactivator. (A) <i>Drosophila</i> EYA contains two conserved regions, the ED2 and ED. The P/S/T-rich region includes both the ED2 and the two MAPK phosphoacceptor sites. (B) Gal4DBD-EYA fusions were used to assay the ability of EYA to activate transcription from a <i>UAS-luciferase</i> reporter gene. Transactivation potentials were calculated by taking the luciferase/β-galactosidase activity ratio for each construct and were plotted relative to the activity of the Gal4DBD vector alone. As shown in panel B, for construct 2, full-length EYA can activate transcription 3.5-fold above Gal4DBD alone. The N terminus of EYA (construct 3), a construct that lacks the ED, is a potent transactivator, activating transcription over 250-fold (note scale change on axis). Gal4DBD-EYA 1-353 (construct 4), a truncation that contains ED2 but removes part of the P/S/T-rich region, reduces transactivation potential to only fivefold. ED2 plus part of the P/S/T-rich region is able to activate transcription at low levels (construct 5), indicating that the entire N terminus is necessary for full transactivation potential. Deletion of the conserved ED2 within the N terminus of EYA (construct 6) sharply reduces transactivation to 41-fold above background, one-fifth the activity of the intact N terminus. Strikingly, deletion of the entire P/S/T-rich region (construct 7) results in complete loss of transactivation potential. (C) Deletion of the EYA domain does not affect protein expression levels. WT, wild type.</div>
</figcaption>
</figure>
<figure class="figure-item "
itemscope itemtype="http://schema.org/ImageObject"
itemprop="associatedMedia"
data-slide-index="1"
data-label-slug="fig-2">
<a class="figure-link"
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec45/180989/6522e6d62d15/mb1731947002.jpg"
itemprop="contentUrl"
aria-describedby="figure-caption-1"
role="button"
data-image-width="424"
data-image-height="855"
data-image-alt="FIG. 2."
data-pmc-id="PMC180989"
data-figure-id="f2">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-1"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec45/180989/fccf6644a32e/mb1731947002.gif"
alt="FIG. 2." />
</a>
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="424">
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="855">
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
<div class="caption-wrap">
<strong class="figure-label">
<p> FIG. 2. </p>
</strong>
<div class="figure-caption-contents"><p> RAS/MAPK signaling activates EYA transactivation.… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> FIG. 2. </p>
</strong>
<div class="figure-caption-contents"><p> RAS/MAPK signaling activates EYA transactivation. Transactivation via Gal4DBD-EYA ΔED is increased significantly but… </p></div>
</div>
<figcaption id="figure-caption-1" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
FIG. 2.
</strong>
<div class="figure-caption-contents">RAS/MAPK signaling activates EYA transactivation. Transactivation via Gal4DBD-EYA ΔED is increased significantly but variably upon the addition of RAS<sup>V12</sup>. Mutations of the MAPK phosphoacceptors to alanine (EYA<sup>S-A</sup>) to prevent phosphorylation, or to aspartic or glutamic acid (EYA<sup>S-D/E</sup>) to mimic phosphorylation, both increase Gal4DBD-EYA ΔED transactivation activity, suggesting that these sites are important for regulation of EYA transactivation potential. Taken with the increase seen upon addition of RAS<sup>V12</sup>, we conclude that RAS signaling can increase EYA transactivation potential.</div>
</figcaption>
</figure>
<figure class="figure-item "
itemscope itemtype="http://schema.org/ImageObject"
itemprop="associatedMedia"
data-slide-index="2"
data-label-slug="fig-3">
<a class="figure-link"
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec45/180989/ed3efda797a5/mb1731947003.jpg"
itemprop="contentUrl"
aria-describedby="figure-caption-2"
role="button"
data-image-width="476"
data-image-height="886"
data-image-alt="FIG. 3."
data-pmc-id="PMC180989"
data-figure-id="f3">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-2"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec45/180989/dcc67fee5fc1/mb1731947003.gif"
alt="FIG. 3." />
</a>
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="476">
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="886">
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
<div class="caption-wrap">
<strong class="figure-label">
<p> FIG. 3. </p>
</strong>
<div class="figure-caption-contents"><i> ARE </i> - <i> luciferase </i> is responsive…</div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> FIG. 3. </p>
</strong>
<div class="figure-caption-contents"><i> ARE </i> - <i> luciferase </i> is responsive to the EYA-SO transcription factor. (A) EYA and…</div>
</div>
<figcaption id="figure-caption-2" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
FIG. 3.
</strong>
<div class="figure-caption-contents"><i>ARE</i>-<i>luciferase</i> is responsive to the EYA-SO transcription factor. (A) EYA and SO alone do not affect transcription of the <i>ARE-luciferase</i> reporter gene, but together can activate transcription 27-fold. Full-length EYA ΔED2 is unable to fully activate transcription of this gene, and neither is a construct missing the entire P/S/T-rich region, EYA Δ223-438. This construct was not expressed at the same level as wild-type EYA (EYA<sup>WT</sup>), so we transfected two (++) and three (+++) times the amount of plasmid to raise protein levels to and above the levels of EYA. These levels still do not activate <i>ARE-luciferase</i>. (B) Quantitative Western blotting shows that EYA (lane 1) and EYA ΔED2 (lane 2) are expressed at similar levels, while the same amount of EYA Δ223-438 plasmid (lane 3) is not. However, transfection of two and three times more EYA Δ223-438 plasmid results in robust expression, as shown in lanes 4 and 5. (C) EYA and SO show a strong interaction in an S2-2H assay. The deletions in EYA do not affect interactions with SO, and in fact, EYA Δ223-438 appears to have a stronger interaction with SO. DAC does not interact with EYA in S2-2H assays. (D) Overexpression of EYA using the 57A1dpp-Gal4 driver causes ectopic eye induction in over 98% of animals (<i>n</i> = 413). Overexpression of EYA ΔED2 results in ectopic eyes in only 35% of animals (<i>n</i> = 506). Deletion of the entire P/S/T-rich region, EYA Δ223-438, results in a protein that can only rarely induce ectopic eyes, seen in only 1.5% of animals examined (<i>n</i> = 204).</div>
</figcaption>
</figure>
<figure class="figure-item "
itemscope itemtype="http://schema.org/ImageObject"
itemprop="associatedMedia"
data-slide-index="3"
data-label-slug="fig-4">
<a class="figure-link"
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec45/180989/7b710c3885c4/mb1731947004.jpg"
itemprop="contentUrl"
aria-describedby="figure-caption-3"
role="button"
data-image-width="644"
data-image-height="325"
data-image-alt="FIG. 4."
data-pmc-id="PMC180989"
data-figure-id="f4">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-3"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec45/180989/f629151e8d22/mb1731947004.gif"
alt="FIG. 4." />
</a>
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="644">
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="325">
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
<div class="caption-wrap">
<strong class="figure-label">
<p> FIG. 4. </p>
</strong>
<div class="figure-caption-contents"><p> EYA-EYA interactions are mediated by… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> FIG. 4. </p>
</strong>
<div class="figure-caption-contents"><p> EYA-EYA interactions are mediated by the EYA N terminus. Using the S2-2H system,… </p></div>
</div>
<figcaption id="figure-caption-3" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
FIG. 4.
</strong>
<div class="figure-caption-contents">EYA-EYA interactions are mediated by the EYA N terminus. Using the S2-2H system, Gal4DBD-EYA fusions shown on the left were coexpressed with (+) and without () full-length Gal4AD-EYA. Full-length EYA interacts with itself sevenfold above the background level. This interaction is mediated by aa 223 to 317, because all constructs that contain this minimal region can interact with Gal4AD-EYA. Strikingly, Gal4DBD-EYA 2-353 and Gal4DBD-EYA ΔED2 (constructs 4 and 6) show a more than threefold-stronger interaction than that of full-length EYA. The Gal4DBD-ED fusion (construct 7) does not interact with Gal4AD-EYA, consistent with our finding that the EYA N terminus mediates this interaction.</div>
</figcaption>
</figure>
<figure class="figure-item "
itemscope itemtype="http://schema.org/ImageObject"
itemprop="associatedMedia"
data-slide-index="4"
data-label-slug="fig-5">
<a class="figure-link"
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec45/180989/894ad8c5876f/mb1731947005.jpg"
itemprop="contentUrl"
aria-describedby="figure-caption-4"
role="button"
data-image-width="526"
data-image-height="1398"
data-image-alt="FIG. 5."
data-pmc-id="PMC180989"
data-figure-id="f5">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-4"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec45/180989/7e67d772b0c1/mb1731947005.gif"
alt="FIG. 5." />
</a>
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="526">
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="1398">
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
<div class="caption-wrap">
<strong class="figure-label">
<p> FIG. 5. </p>
</strong>
<div class="figure-caption-contents"><p> The EYA-SO transcription factor is… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> FIG. 5. </p>
</strong>
<div class="figure-caption-contents"><p> The EYA-SO transcription factor is regulated by phosphorylation. (A) As shown in Fig.… </p></div>
</div>
<figcaption id="figure-caption-4" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
FIG. 5.
</strong>
<div class="figure-caption-contents">The EYA-SO transcription factor is regulated by phosphorylation. (A) As shown in Fig. 3, the EYA-SO transcription factor can activate expression of <i>ARE-luciferase</i>. This expression is not affected by addition of RAS<sup>V12</sup> nor upon mutation of the MAPK phosphoacceptor sites to alanine (EYA<sup>S-A</sup>). A striking increase in activation is seen when the EYA<sup>S-D/E</sup> phosphomimetic mutant is used, showing that phosphorylation acts to increase EYA transactivation potential. That RAS<sup>V12</sup> itself does not produce the same increase on wild-type EYA (WT) in this assay suggests that RAS signaling may have multiple effects on the RD gene network and in particular may negatively regulate SO. (B) EYA phosphoacceptor mutations do not affect protein expression levels.</div>
</figcaption>
</figure>
<figure class="figure-item "
itemscope itemtype="http://schema.org/ImageObject"
itemprop="associatedMedia"
data-slide-index="5"
data-label-slug="fig-6">
<a class="figure-link"
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec45/180989/8b2f293bfd33/mb1731947006.jpg"
itemprop="contentUrl"
aria-describedby="figure-caption-5"
role="button"
data-image-width="400"
data-image-height="380"
data-image-alt="FIG. 6."
data-pmc-id="PMC180989"
data-figure-id="f6">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-5"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec45/180989/7594112f04e3/mb1731947006.gif"
alt="FIG. 6." />
</a>
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="400">
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="380">
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
<div class="caption-wrap">
<strong class="figure-label">
<p> FIG. 6. </p>
</strong>
<div class="figure-caption-contents"><p> The EYA-SO transcription factor is… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> FIG. 6. </p>
</strong>
<div class="figure-caption-contents"><p> The EYA-SO transcription factor is negatively regulated by interactions with GROUCHO. (A) When… </p></div>
</div>
<figcaption id="figure-caption-5" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
FIG. 6.
</strong>
<div class="figure-caption-contents">The EYA-SO transcription factor is negatively regulated by interactions with GROUCHO. (A) When coexpressed with EYA and SO, GRO is a repressor of the EYA-SO transcription factor. (B) Lanes 1 and 2 show that MYC-EYA and GRO are not pulled down by anti-Flag beads. In lane 3, IP of SO can co-IP EYA. Lane 4 shows that IP of SO can co-IP EYA but not GRO; however, in lane 5, we see that without EYA, GRO can associate with SO. Thus, co-IP of GRO with SO is disrupted by cotransfection of EYA. This result does not seem to be due to direct competition between EYA and SO for GRO, because IP of EYA cannot co-IP GRO. All proteins were expressed at similar levels in crude cell lysates (data not shown).</div>
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<h2 class="title">
Related information
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Cited in Books
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Gene
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Gene (GeneRIF)
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MedGen
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ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=12917324&ordinalpos=1&linkpos=5">
MedGen (Bookshelf cited)
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Protein (RefSeq)
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Grants and funding
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LinkOut - more resources
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<ul class="linkout-list"><li><h3 class="linkout-category">Full Text Sources</h3><ul class="linkout-category-links"><li><a
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