73-kDa heat shock cognate protein interacts directly with P27Kip1, a cyclin-dependent kinase inhibitor, during G1/S transition.
Although heat shock proteins (HSPs) were discovered as inducible proteins by the physical stress to protect cells, recent evidence has suggested that HSPs are likely involved in cell cycle control under normal conditions without stress. In the present study, we demonstrated that 73hsc (heat shock cognate protein), which belongs to the HSP70 family of molecular chaperones, interacts with P27Kip1, an inhibitor of cyclin-dependent kinase, during G1/S transition. 73hsc was detected in the immunoprecipitates with anti-P27Kip1 antibody and, vice versa, P27Kip1 was present in the immunoprecipitates with anti-73hsc antibody by Western blotting using growth-stimulated rat thyroid FRTL-5 cells. This complex formation of 73hsc and P27Kip1 was cell cycle dependent and its maximum formation was observed at G1/S transition where the level of P27Kip1 dramatically decreased. ATP dissociated this complex formation in a dose-dependent manner. These data indicated that 73hsc might be involved in the cell cycle progression through the regulation of cell cycle regulators such as P27Kip1.
Nakamura
S
S
Second Department of Internal Medicine, Chiba University Medical School, Inohana-cho, Chiba, Chuou-ku, 260, Japan.
Tatuno
I
I
Noguchi
Y
Y
Kitagawa
M
M
Kohn
L D
LD
Saito
Y
Y
Hirai
A
A
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002460:Cell Line; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D016193:G1 Phase / Q000187:drug effects; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011233:Precipitin Tests; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D016196:S Phase / Q000187:drug effects; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D013972:Thyrotropin / Q000494:pharmacology; D013997:Time Factors; D025521:Tumor Suppressor Proteins
D002352:Carrier Proteins; C493962:Cdkn1b protein, rat; D018797:Cell Cycle Proteins; D016213:Cyclins; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C494373:Hspa8 protein, rat; D008869:Microtubule-Associated Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; C022571:adenosine 5'-O-(3-thiotriphosphate); D000244:Adenosine Diphosphate; D007334:Insulin-Like Growth Factor I; D000255:Adenosine Triphosphate; D013972:Thyrotropin; D018844:Cyclin-Dependent Kinases