Role of the cochaperone Tpr2 in Hsp90 chaperoning.
The molecular chaperones Hsp90 and Hsp70 are highly regulated by various cochaperones that participate in the activation of steroid receptors. Here we study Tpr2 (also called DjC7), a TPR domain-containing type III J protein implicated in steroid receptor chaperoning. We propose that Tpr2 plays a role in the Hsp90-dependent chaperoning of the progesterone receptor (PR). Tpr2 overexpression or knockdown resulted in slight reductions in PR transcriptional activity in HeLa cells. Immunoprecipitation and pulldown experiments indicated that Tpr2 associates with Hsp90 and Hsp70 complexes, some of which also contain the PR. Tpr2 can bind Hsp90 and Hsp70 simultaneously, which is also a property of the cochaperone Hop. However, unlike Hop, Tpr2 binding to Hsp70 in the presence of Hsp90 is ATP-dependent, and Tpr2 cannot replace Hop in Hsp90 chaperoning in vitro or in vivo. While Tpr2 was not detected as a component of PR heterocomplexes in cell lysates, purified Tpr2 bound the PR readily. Surprisingly, Tpr2 replaced type I and II J proteins in the Hsp90-dependent chaperoning of the PR and the protein kinase, Chk1. Unlike other J proteins, Tpr2 promoted the accumulation of Hsp70 in PR heterocomplexes in the presence of Hsp90. Thus, Tpr2 has the potential to regulate PR chaperoning.
Moffatt
Nela S Cintrón
NS
Department of Biochemistry and Molecular Biology, Mayo Graduate School, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Bruinsma
Elizabeth
E
Uhl
Cindy
C
Obermann
Wolfgang M J
WM
Toft
David
D
D000255:Adenosine Triphosphate / Q000378:metabolism; D050956:HSP40 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006360:Heat-Shock Proteins; D006801:Humans; D047468:Immunoprecipitation; D008954:Models, Biological; D018832:Molecular Chaperones; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D014158:Transcription, Genetic
C485782:DNAJC7 protein, human; D050956:HSP40 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D034741:RNA, Small Interfering; D011980:Receptors, Progesterone; D011994:Recombinant Proteins; D000255:Adenosine Triphosphate