CREB-binding protein sequestration by expanded polyglutamine
- PMID: 10958659
- DOI: 10.1093/hmg/9.14.2197
CREB-binding protein sequestration by expanded polyglutamine
Abstract
Spinal and bulbar muscular atrophy (SBMA) is one of eight inherited neurodegenerative diseases known to be caused by CAG repeat expansion. The expansion results in an expanded polyglutamine tract, which likely confers a novel, toxic function to the affected protein. Cell culture and transgenic mouse studies have implicated the nucleus as a site for pathogenesis, suggesting that a critical nuclear factor or process is disrupted by the polyglutamine expansion. In this report we present evidence that CREB-binding protein (CBP), a transcriptional co-activator that orchestrates nuclear response to a variety of cell signaling cascades, is incorporated into nuclear inclusions formed by polyglutamine-containing proteins in cultured cells, transgenic mice and tissue from patients with SBMA. We also show CBP incorporation into nuclear inclusions formed in a cell culture model of another polyglutamine disease, spinocerebellar ataxia type 3. We present evidence that soluble levels of CBP are reduced in cells expressing expanded polyglutamine despite increased levels of CBP mRNA. Finally, we demonstrate that over-expression of CBP rescues cells from polyglutamine-mediated toxicity in neuronal cell culture. These data support a CBP-sequestration model of polyglutamine expansion disease.
Similar articles
-
[Triplet repeat disease, with particular emphasis of spinal and bulbar muscular atrophy (SBMA)].Rinsho Shinkeigaku. 2000 Dec;40(12):1193-5. Rinsho Shinkeigaku. 2000. PMID: 11464455 Japanese.
-
Ataxin-3 protein modification as a treatment strategy for spinocerebellar ataxia type 3: removal of the CAG containing exon.Neurobiol Dis. 2013 Oct;58:49-56. doi: 10.1016/j.nbd.2013.04.019. Epub 2013 May 6. Neurobiol Dis. 2013. PMID: 23659897
-
Caspase-mediated proteolysis of the polyglutamine disease protein ataxin-3.J Neurochem. 2004 May;89(4):908-18. doi: 10.1111/j.1471-4159.2004.02369.x. J Neurochem. 2004. PMID: 15140190
-
Polyglutamine diseases: the special case of ataxin-3 and Machado-Joseph disease.Prog Neurobiol. 2011 Sep 15;95(1):26-48. doi: 10.1016/j.pneurobio.2011.06.007. Epub 2011 Jun 28. Prog Neurobiol. 2011. PMID: 21740957 Review.
-
Mouse models of Machado-Joseph disease and other polyglutamine spinocerebellar ataxias.NeuroRx. 2005 Jul;2(3):480-3. doi: 10.1602/neurorx.2.3.480. NeuroRx. 2005. PMID: 16389311 Free PMC article. Review.
Cited by
-
Spinal and bulbar muscular atrophy: pathogenesis and clinical management.Oral Dis. 2014 Jan;20(1):6-9. doi: 10.1111/odi.12121. Epub 2013 May 9. Oral Dis. 2014. PMID: 23656576 Free PMC article. Review.
-
Phthalate-Induced Fetal Leydig Cell Dysfunction Mediates Male Reproductive Tract Anomalies.Front Pharmacol. 2019 Nov 6;10:1309. doi: 10.3389/fphar.2019.01309. eCollection 2019. Front Pharmacol. 2019. PMID: 31780936 Free PMC article. Review.
-
CRE-mediated transcription is increased in Huntington's disease transgenic mice.J Neurosci. 2004 Jan 28;24(4):791-6. doi: 10.1523/JNEUROSCI.3493-03.2004. J Neurosci. 2004. PMID: 14749423 Free PMC article.
-
The Gln-Ala repeat transcriptional activator CA150 interacts with huntingtin: neuropathologic and genetic evidence for a role in Huntington's disease pathogenesis.Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):1811-6. doi: 10.1073/pnas.98.4.1811. Epub 2001 Jan 30. Proc Natl Acad Sci U S A. 2001. PMID: 11172033 Free PMC article.
-
Role of heat shock proteins during polyglutamine neurodegeneration: mechanisms and hypothesis.J Mol Neurosci. 2004;23(1-2):69-96. doi: 10.1385/JMN:23:1-2:069. J Mol Neurosci. 2004. PMID: 15126694 Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
