Direct interaction of p21 cyclin-dependent kinase inhibitor with the retinoblastoma tumor suppressor protein.
The p21CKI forms a physical complex with the retinoblastoma protein (pRb) both in vitro and in vivo. The A/B pocket region of pRb and the N-terminal region of p21 were indispensable for this interaction. Among p21 family members, p57, but not p27, associated with pRb. Overexpression of cyclin D1, Cdk4, and E2F1 in the cells expressing pRb and p21 did not perturb the interaction between p21 and pRb. Coexpression of p21 in cells expressing pRb, cyclin D1, and Cdk4 prevented pRb hyperphosphorylation by cyclin D1/Cdk4. On the other hand, hyperphosphorylation of pRb by an excess amount of cyclin/Cdk disrupted pRb/p21 complex formation in vitro. These findings suggest that pRb may be dynamically regulated by the relative binding and activities of p21 and Cdks.
Nakanishi
M
M
Department of Geriatric Research, National Institute for Longevity Sciences, 36-3 Gengo, Morioka-cho, Obu, Aichi, 474, Japan. mkt-naka@med.nagoya-cu.ac.jp
Kaneko
Y
Y
Matsushime
H
H
Ikeda
K
K
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002460:Cell Line; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D016213:Cyclins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D010766:Phosphorylation; D011485:Protein Binding; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D056465:Retinoblastoma-Binding Protein 1; D018411:Spodoptera; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
C493956:CDKN1A protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D016160:Retinoblastoma Protein; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors; D019938:Cyclin D1; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases