Human cyclophilin 40 is a heat shock protein that exhibits altered intracellular localization following heat shock

Mark, PJ, Ward, BK, Kumar, P, Lahooti, H, Minchin, RF and Ratajczak, T (2001) Human cyclophilin 40 is a heat shock protein that exhibits altered intracellular localization following heat shock. Cell Stress & Chaperones, 6 1: 59-70. doi:10.1379/1466-1268(2001)006<0059:HCIAHS>2.0.CO;2


Author Mark, PJ
Ward, BK
Kumar, P
Lahooti, H
Minchin, RF
Ratajczak, T
Title Human cyclophilin 40 is a heat shock protein that exhibits altered intracellular localization following heat shock
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<0059:HCIAHS>2.0.CO;2
Volume 6
Issue 1
Start page 59
End page 70
Total pages 12
Place of publication Storrs
Publisher Cell Stress Soc International
Language eng
Abstract The unactivated steroid receptors are chaperoned into a conformation that is optimal for binding hormone by a number of heat shock proteins, including Hsp90, Hsp70, Hsp40, and the immunophilin, FKBP52 (Hsp56). Together with its partner cochaperones, cyclophilin 40 (CyP40) and FKBP51, FKBP52 belongs to a distinct group of structurally related immunophilins that modulate steroid receptor function through their association with Hsp90. Due to the structural similarity between the component immunophilins, FKBP52 and cyclophilin 40, we decided to investigate whether CyP40 is also a heat shock protein. Exposure of MCF-7 breast cancer cells to elevated temperatures (42 degreesC for 3 hours) resulted in a 75-fold increase in CyP40 mRNA levels, but no corresponding increase in CyP40 protein expression, even after 7 hours of heat stress. The use of cycloheximide to inhibit protein synthesis revealed that in comparison to MCF-7 cells cultured at 37 degreesC, those exposed to heat stress (42 degreesC for 3 hours) displayed an elevated rate of degradation of both CyP40 and FKBP52 proteins. Concomitantly, the half-life of the CyP40 protein was reduced from more than 24 hours to just over 8 hours following heat shock. As no alteration in CyP40 protein levels occurred in cells exposed to heat shock, an elevated rate of degradation would imply that CyP40 protein was synthesized at an increased rate. hence the designation of human CyP40 as a heat shock protein. Application of heat stress elicited a marked redistribution of CyP40 protein in MCF-7 cells from a predominantly nucleolar localization, with some nuclear and cytoplasmic staining, to a pattern characterized by a pronounced nuclear accumulation of CyP40, with no distinguishable nucleolar staining. This increase in nuclear CyP40 possibly resulted from a redistribution of cytoplasmic and nucleolar CyP40, as no net increase in CyP40 expression levels occurred in response to stress. Exposure of MCF-7 cells to actinomycin D for 4 hours resulted in the translocation of the nucleolar marker protein, B23, from the nucleolus, with only a small reduction in nucleolar CyP40 levels. Under normal growth conditions, MCF-7 cells exhibited an apparent colocalization of CyP40 and FKBP52 within the nucleolus.
Keyword Cell Biology
Tetratricopeptide Repeat Domain
Steroid-receptor Complexes
Gene-expression
Transcription Factor
Mammalian-cells
Glucocorticoid Receptor
Nucleolar Localization
Progesterone-receptor
Molecular-cloning
Cyclosporine-a
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 34 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 38 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Mon, 13 Aug 2007, 22:17:26 EST