dc.contributor.author |
Nguyen, Minh Tu |
|
dc.contributor.author |
Csermely, Péter |
|
dc.contributor.author |
Sőti, Csaba |
|
dc.date.accessioned |
2017-03-28T10:28:35Z |
|
dc.date.available |
2017-03-28T10:28:35Z |
|
dc.date.issued |
2013 |
|
dc.identifier |
84887572789 |
|
dc.identifier.citation |
pagination=1654-1663;
journalVolume=20;
journalIssueNumber=12;
journalTitle=CELL DEATH AND DIFFERENTIATION; |
|
dc.identifier.uri |
http://repo.lib.semmelweis.hu//handle/123456789/2474 |
|
dc.identifier.uri |
doi:10.1038/cdd.2013.129 |
|
dc.description.abstract |
Adipose tissue dysregulation has a major role in various human diseases. The peroxisome proliferator-activated receptor-γ (PPARγ) is a key regulator of adipocyte differentiation and function, as well as a target of insulin-sensitizing drugs. The Hsp90 chaperone stabilizes a diverse set of signaling 'client' proteins, thereby regulates various biological processes. Here we report a novel role for Hsp90 in controlling PPARγ stability and cellular differentiation. Specifically, we show that the Hsp90 inhibitors geldanamycin and novobiocin efficiently impede the differentiation of murine 3T3-L1 preadipocytes. Geldanamycin at higher concentrations also inhibits the survival of both developing and mature adipocytes, respectively. Further, Hsp90 inhibition disrupts an Hsp90-PPARγ complex, leads to the destabilization and proteasomal degradation of PPARγ, and inhibits the expression of PPARγ target genes, identifying PPARγ as an Hsp90 client. A similar destabilization of PPARγ and a halt of adipogenesis also occur in response to protein denaturing stresses caused by a single transient heat-shock or proteasome inhibition. Recovery from stress restores PPARγ stability and adipocyte differentiation. Thus, our findings reveal Hsp90 as a critical stress-responsive regulator of adipocyte biology and offer a potential therapeutic target in obesity and the metabolic syndrome.Cell Death and Differentiation advance online publication, 4 October 2013; doi:10.1038/cdd.2013.129. |
|
dc.relation.ispartof |
urn:issn:1350-9047 |
|
dc.title |
Hsp90 chaperones PPARγ and regulates differentiation and survival of 3T3-L1 adipocytes |
|
dc.type |
Journal Article |
|
dc.date.updated |
2015-11-20T13:16:18Z |
|
dc.language.rfc3066 |
en |
|
dc.identifier.mtmt |
2437212 |
|
dc.identifier.wos |
000327010600009 |
|
dc.identifier.pubmed |
24096869 |
|
dc.contributor.department |
SE/AOK/I/Orvosi Vegytani, Molekuláris Biológiai és Patobiokémiai Intézet |
|
dc.contributor.institution |
Semmelweis Egyetem |
|