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- Title
TGFβ influences Myc, Miz-1 and Smad to control the CDK inhibitor p15<sup>INK4b</sup>.
- Authors
Seoane, Joan; Pouponnot, Celio; Staller, Peter; Schader, Manuela; Eilers, Martin; Massagué, Joan
- Abstract
Transforming growth factor-β (TGFβ) is a cytokine that arrests epithelial cell division by switching off the proto-oncogene c-myc and rapidly switching on cyclin-dependent kinase (CDK) inhibitors such as p15[sup INK4b]. Gene responses to TGFβ involve Smad transcription factors that are directly activated by the TGFβ receptor. Why downregulation of cmyc expression by TGFβ is required for rapid activation of p15[sup INK4b] has remained unknown. Here we provide evidence that TGFβ signalling prevents recruitment of Myc to the p15[sup INK4b] transcriptional initiator by Myc-interacting zinc-finger protein 1 (Miz-1). This relieves repression and enables transcriptional activation by a TGFβ-induced Smad protein complex that recognizes an upstream p15[sup INK4b] promoter region and contacts Miz-1. Thus, two separate TGFβ-dependent inputs — Smad-mediated transactivation and relief of repression by Myc — keep tight control over p15[sup INK4b] activation.
- Publication
Nature Cell Biology, 2001, Vol 3, Issue 4, p400
- ISSN
1465-7392
- Publication type
Academic Journal
- DOI
10.1038/35070086