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PMID: 9001212 Published · ppublish English Comparative Study Journal Article Research Support, U.S. Gov't, P.H.S.

Molecular cloning of human FKBP51 and comparisons of immunophilin interactions with Hsp90 and progesterone receptor.

Molecular and cellular biology ·Vol. 17 ·No. 2 ·1997-02-00 ·Pages 594-603

Nair SC, Rimerman RA, Toran EJ, Chen S, Prapapanich V, Butts RN, Smith DF

Abstract

A cDNA for human FKBP51 has been cloned and sequenced, and protein products have been expressed in both in vitro and bacterial systems. The deduced amino acid sequence for human FKBP51 is 90% identical to sequences of recently described murine proteins and is 55% identical to the sequence of human FKBP52. Human FKBP51 mRNA is expressed in a wide range of tissues, and the protein has peptidylprolyl isomerase activity that is inhibited by FK506 but not cyclosporine. FKBP51 is the same as a previously described progesterone receptor-associated immunophilin that, similar to FKBP52 and cyclophilin 40, is an Hsp90-binding protein and appears in functionally mature steroid receptor complexes along with Hsp90 and p23. Each of the three receptor-associated immunophilins displays interactions with progesterone receptor that are more dynamic than Hsp90-receptor interactions. Whereas FKBP52 and FKBP51 compete about equally well for binding to Hsp90 in a purified system, FKBP51 accumulates preferentially in progesterone receptor complexes assembled in a cell-free system. This observation provides a precedent for differential interactions between Hsp90-associated immunophilins and target proteins such as steroid receptors.

MeSH Terms
Amino Acid Isomerases/metabolism Amino Acid Sequence Animals Carrier Proteins/genetics,metabolism Cell-Free System Chickens Cloning, Molecular DNA, Complementary/genetics DNA-Binding Proteins/genetics,metabolism Enzyme Inhibitors/pharmacology HSP90 Heat-Shock Proteins/isolation & purification,metabolism Heat-Shock Proteins/genetics,metabolism Humans Molecular Sequence Data Organ Specificity Peptidylprolyl Isomerase Protein Binding RNA, Messenger/analysis Receptors, Progesterone/metabolism Recombinant Fusion Proteins Sequence Homology, Amino Acid Tacrolimus/pharmacology Tacrolimus Binding Proteins
Chemicals
Carrier Proteins DNA, Complementary DNA-Binding Proteins Enzyme Inhibitors HSP90 Heat-Shock Proteins Heat-Shock Proteins RNA, Messenger Receptors, Progesterone Recombinant Fusion Proteins Amino Acid Isomerases Tacrolimus Binding Proteins Peptidylprolyl Isomerase Tacrolimus
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Nair S C
Department of Pharmacology, University of Nebraska Medical Center, Omaha 68198-6260, USA.
Rimerman R A
Toran E J
Chen S
Prapapanich V
Butts R N
Smith D F
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.17.2.594
Published
1997-02-00
Pages
594-603
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC231784
Subset
IM
Grants
NIDDK NIH HHS · R01 DK48218 · United States
Databases
GENBANK
L11667, M88279, U16959, U36220, U42031
External Links
PubMed source DOI: 10.1128/MCB.17.2.594 PMC Full Text View journal details
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