Linked Life Data

15836624

Source:http://linkedlifedata.com/resource/pubmed/id/15836624

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2005-4-19
pubmed:abstractText
On the basis of the hypothesis that the interaction of mutant proteins with expanded polyglutamine stretches with transcriptional co-activator, TAFII130, leads to transcriptional dysregulation, the transcriptional activation of c-Fos and its suppression by expanded polyglutamine stretches was investigated. The phosphorylation of cAMP-responsive element binding protein (CREB) and induction of c-Fos in response to cAMP were strongly suppressed in Neuro2a cells expressing expanded polyglutamine. The suppression of CREB-dependent transcriptional activation was reversibly rescued by increasing the concentration of cAMP. Expanded polyglutamine-induced cytotoxicity was also substantially suppressed by augmenting CREB-dependent transcriptional activation with a high concentration of cAMP. FR901228, a histone deacetylase inhibitor, was also demonstrated as rescuing the expanded polyglutamine-induced suppression of CREB phosphorylation and c-Fos expression. Furthermore, nuclear fragmentation was significantly suppressed by FR901228. The co-expression of dominant-negative CREB vectors considerably abrogated the suppressive effect of cAMP and FR901228 on the expanded polyglutamine-induced nuclear fragmentation, suggesting that these compounds suppress polyglutamine-induced cytotoxicity, largely, via the enhancement of CREB-dependent transcriptional activation. These findings suggest that the interference of CREB-dependent transcriptional activation by expanded polyglutamine stretches is involved in the pathogenetic mechanisms underlying neurodegeneration, and that the augmentation of CREB-dependent transcriptional activation is a potential strategy in treating polyglutamine diseases.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-3042
pubmed:author
pubmed:issnType
Print
pubmed:volume
93
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
654-63
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Interference of CREB-dependent transcriptional activation by expanded polyglutamine stretches--augmentation of transcriptional activation as a potential therapeutic strategy for polyglutamine diseases.
pubmed:affiliation
Department of Neurology, Brain Research Institute, Niigata University, Niigata, Japan. m-shimohata@pop17.odn.ne.jp
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't