Regulation of the Hsp90-binding immunophilin, cyclophilin 40, is mediated by multiple sites for CA-binding protein (GABP)

Kumar, P, Ward, BK, Minchin, RF and Ratajczak, T (2001) Regulation of the Hsp90-binding immunophilin, cyclophilin 40, is mediated by multiple sites for CA-binding protein (GABP). Cell Stress & Chaperones, 6 1: 78-91. doi:10.1379/1466-1268(2001)006<0078:ROTHBI>2.0.CO;2


Author Kumar, P
Ward, BK
Minchin, RF
Ratajczak, T
Title Regulation of the Hsp90-binding immunophilin, cyclophilin 40, is mediated by multiple sites for CA-binding protein (GABP)
Journal name Cell Stress & Chaperones   Check publisher's open access policy
ISSN 1355-8145
Publication date 2001-01-01
Sub-type Article (original research)
DOI 10.1379/1466-1268(2001)006<0078:ROTHBI>2.0.CO;2
Volume 6
Issue 1
Start page 78
End page 91
Total pages 14
Place of publication Storrs
Publisher Cell Stress Soc International
Language eng
Abstract Within steroid receptor heterocomplexes the large tetraticopeptide repeat-containing immunophilins, cyclophilin 40 (CyP40), FKBP51, and FKBP52, target a common interaction site in heat shock protein 90 (HspSO) and act coordinately with HspSO to modulate receptor activity. The reversible nature of the interaction between the immunophilins and HspSO suggests that relative cellular abundance might be a key determinant of the immunophilin component within steroid receptor complexes. To investigate CyP40 gene regulation, we have isolated a fi-kilobase (kb) 5 ' -flanking region of the human gene and demonstrated that a similar to 50 base pair (bp) sequence adjacent to the transcription start site is essential for CyP40 basal expression. Three tandemly arranged Ets sites within this critical region were identified as binding elements for the multimeric Ets-related transcription factor, GA binding protein (GABP). Functional studies of this proximal promoter sequence, in combination with mutational analysis, confirmed these sites to be crucial for basal promoter function. Furthermore, overexpression of both GABP alpha and GABP beta subunits in Cos1 cells resulted in increased endogenous CyP40 mRNA levels. Significantly, a parallel increase in FKBP52 mRNA expression was not observed, highlighting an important difference in the mode of regulation of the CyP40 and FKBP52 genes. Our results identify GABP as a key regulator of CyP40 expression. GAFF is a common target of mitogen and stress-activated pathways and may integrate these diverse extracellular signals to regulate CyP40 gene expression.
Keyword Cell Biology
Heat-shock-protein
Progesterone-receptor Complexes
Glucocorticoid Receptor
Transcription Factor
Estrogen-receptor
Fk506-binding Protein
Mutational Analysis
Molecular-cloning
Dna Methylation
Gene-expression
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Biomedical Sciences Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 17 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 18 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Mon, 13 Aug 2007, 22:17:28 EST