p53, through p21 (WAF1/CIP1), induces cyclin D1 synthesis.
Cells induced to accumulate the p53 tumor suppressor protein have been shown to arrest in G1. This arrest is characterized by accumulation of the cyclin-dependent kinase inhibitor p21 (WAF1/CIP1) and of under-phosphorylated forms of retinoblastoma protein. We show here that accumulation of the wild-type p53 protein in either human or murine cells markedly increases expression of cyclin D1. The induction of cyclin D1 can also be mediated by a target of p53, the p21 (WAF1/CIP1) inhibitor of cyclin-dependent kinases. The relationship between the induction of cyclin D1 and G1 arrest defines a new cellular response to p53.
Chen
X
X
Department of Biological Sciences, Columbia University, New York, New York 10027, USA.
Bargonetti
J
J
Prives
C
C
D000818:Animals; D002166:Camptothecin / Q000494:pharmacology; D002460:Cell Line; D019938:Cyclin D1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis* / Q000502:physiology*; D004249:DNA Damage; D016193:G1 Phase; D006801:Humans; D051379:Mice; D015513:Oncogene Proteins / Q000096:biosynthesis*; D047428:Protein Kinase Inhibitors; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D015513:Oncogene Proteins; D047428:Protein Kinase Inhibitors; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; D002166:Camptothecin