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p53, through p21 (WAF1/CIP1), Induces Cyclin D1 Synthesis¹

Department of Biological Sciences, Columbia University, New York, New York 10027

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 underphosphorylated 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.

¹ This work was supported by a grant from U.S. Army breast cancer program (DAMD17-94-J-4275 to C. P.) X. C. was supported by a postdoctoral fellowship from the U.S. Army breast cancer program (DAMD17-94-J-4142).

² To whom requests for reprints should be addressed.

Received 6/29/95. Accepted 8/18/95.

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