Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2008-6-24
pubmed:abstractText
HSP90 chaperones are transducer proteins of many signaling pathways in cells. Using a highly specific inhibitor, geldanamycin (GA), an increasing number of the HSP90 client proteins have been identified. Nevertheless, there is little information on the differential transactivation of the two isoforms of the hsp90 genes, hsp90alpha and beta, in cells under stress conditions. Here, we demonstrate the differential expression of the HSP90 isoforms, HSP90alpha and beta, in rat gliosarcoma 9L cells using a modified SDS-PAGE system that allowed us to distinguish the isoforms. We subsequently assessed the transcriptional controls involving the transcription elements located in the promoter regions of the hsp90 genes. At the protein level, HSP90alpha is more responsive to GA in terms of rate of de novo synthesis and amount of accumulation, as shown by metabolic-labeling and Western-blotting analyses. Upregulation of the hsp90 genes was demonstrated by real-time qPCR. The promoter elements hsp90alpha-HSE2 and hsp90beta-HSE1 were also identified to be the major transcription elements involved in GA-activated gene expression, as shown by EMSA, whereas the results of supershift showed that the transcription factor HSF1 is also involved. Moreover, EMSA results of analysis of the GC box showed differences in both the initial amounts and inductive response of hsp90s transcripts, whereas analysis of the TATA box showed GA responsiveness in hsp90alpha only. Collectively, these results indicate that GA exerts its regulatory effects through transcription elements including heat-shock elements (HSEs), GC boxes and TATA boxes, resulting in differential transactivation of hsp90alpha and hsp90beta in rat gliosarcoma 9L cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1097-4644
pubmed:author
pubmed:copyrightInfo
2008 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
104
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1286-96
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Concerted actions of multiple transcription elements confer differential transactivation of HSP90 isoforms in geldanamycin-treated 9L rat gliosarcoma cells.
pubmed:affiliation
Department of Life Science, Institute of Biotechnology, National Tsing Hua University, Hsinchu, Taiwan 30013, ROC.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't