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for="query">Enter Search Term(s):</label><div class="search__content"><input autocomplete="off" id="query" name="query" type="text" class="search__input" /><button name="commit" type="submit" value="Search" class="search__button"><span class="visually-hidden">Search</span><svg aria-hidden="true" class="icon icon--search" viewBox="0 0 29 32" width="29" height="32"><use xlink:href="/themes/rf/dist/images/icons/icons.svg?v2#search"></use></svg></button></div></form></div></div></div></div></div></div>
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<article><div class="banner banner--gray banner--compact" style="--banner-background-image: url('/sites/default/files/media/image/2021-03/2015.jpg');--banner-background-focus: 50% 50%"><div class="banner__wrapper"><div class="banner__container"><h2 class="banner__heading">NIH Research Festival</h2><div class="banner__content"><p><strong><time datetime="2015-09-16">September 16</time> – <time datetime="2015-09-18">18, 2015</time></strong></p></div></div></div></div></article>
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<div class="section"><div data-drupal-messages-fallback class="hidden"></div></div><main role="main"><div id="main-content" tabindex="-1"></div><div class="section"><div class="content-sidebar"><div class="content-sidebar__main"><div class="content-sidebar__main-content"><div id="block-mainpagecontent-2"><article><h1>Unveiling the role of C/EBPG as a Master Stress Response Regulator</h1><div class="schedule"><div class="schedule__label"><div class="schedule__label-text"><time datetime="2015-09-17">Thursday, September 17, 2015</time>
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– Poster Session II
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</div></div><div class="schedule__content"><div class="schedule__item"><div class="schedule__time">12:00 – 1:30 p.m.</div><div class="schedule__description"><p><strong>FAES Terrace</strong></p></div><div class="schedule__description"><p><strong>NCI</strong></p></div><div class="schedule__description"><p><strong>CANCER-20</strong></p></div></div></div></div><p><strong>FARE Award Winner</strong></p><h2>Authors</h2><ul><li>MK Mayekar</li><li>CJ Huggins</li><li>N Martin</li><li>KL Saylor</li><li>M Gonit</li><li>P Jailwala</li><li>M Kasoji</li><li>DC Haines</li><li>OA Quinones</li><li>PF Johnson</li></ul><h2>Abstract</h2><p>The integrated stress response (ISR) regulates cellular adaptation to various stresses such as amino acid deprivation and redox imbalances. ISR upregulates the transcription factor ATF4 to activate stress-response genes through association with cis-regulatory sites known as C/EBP:ATF response elements (CAREs) as a heterodimer with a C/EBP partner whose identity remains obscure. Here we show that C/EBPG:ATF4 heterodimers are the predominant CARE-binding species in stressed cells. Similar to ATF4, C/EBPG is also necessary for resistance of MEFs to oxidative stress. Cebpg-/- MEFs show increased levels of reactive oxygen species (ROS) as a consequence of impaired glutathione biosynthesis, as seen in ATF4-deficient MEFs. C/EBPG is required for stress-induced association of ATF4 with CAREs and activation of stress-responsive genes. Also, Cebpg-/- mice show defective eye lens formation, similar to ATF4-deficient mice. Additionally, the absence of C/EBPG causes perinatal mortality due to pulmonary atelectasis which can be rescued by in utero exposure to the antioxidant, N-acetylcysteine. Furthermore, Cebpg-/- mice show reduced incidence of spontaneous solid tumors and increased incidence of B-cell lymphomas. These findings suggests that C/EBPG may be critical for cancer cells to alleviate the hypoxic and nutrient deprivation stress in solid tumors and increased levels of ROS in the absence of C/EBPG may promote genetic lesions required for lymphomagenesis. Increased expression of C/EBPG in tumors has been shown to be associated with poor patient prognosis in several clinical studies. Hence, activation of stress-responsive genes through up-regulation of C/EBPG could be used by cancer cells to mitigate high levels of stress.</p><p><strong>Scientific Focus Area</strong>: Cancer Biology</p><p class="updated"><small>This page was last updated on Friday, March 26, 2021</small></p></article>
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