TGFβ influences myc, miz-1 and smad to control the CDK inhibitor p15INK4b Journal Article
| Authors: | Seoane, J.; Pouponnot, C.; Staller, P.; Schader, M.; Eilers, M.; Massagué, J. |
| Article Title: | TGFβ influences myc, miz-1 and smad to control the CDK inhibitor p15INK4b |
| 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 p15INK4b. Gene responses to TGFβ involve Smad transcription factors that are directly activated by the TGFβ receptor. Why downregulation of c-myc expression by TGFβ is required for rapid activation of p15INK4b has remained unknown. Here we provide evidence that TGFβ signalling prevents recruitment of Myc to the p15INK4b 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 p15INK4b 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 p15INK4b activation. |
| Keywords: | signal transduction; controlled study; carrier protein; dna binding protein; human cell; promoter region; genetics; dna-binding proteins; nonhuman; molecular genetics; cell cycle protein; animal cell; mouse; animal; metabolism; animals; cell cycle proteins; mice; smad protein; smad2 protein; smad3 protein; smad7 protein; transforming growth factor beta; protein protein interaction; transcription initiation; transcription factor; cercopithecus aethiops; cos cells; animalia; transcription factors; gene activation; drug antagonism; molecular sequence data; molecular recognition; nucleotide sequence; myc protein; transactivator protein; gene repression; carrier proteins; tumor suppressor proteins; transactivation; smad3 protein, human; cell strain cos1; cercopithecus; base sequence; gene control; response elements; trans-activators; gene silencing; cyclin-dependent kinase inhibitor p16; oncogene c myc; tumor suppressor protein; cyclin-dependent kinases; cyclin dependent kinase; cyclin dependent kinase inhibitor; proto-oncogene proteins c-myc; dna responsive element; zinc finger protein; zinc fingers; cyclin-dependent kinase inhibitor p15; smad4 protein; cyclin dependent kinase inhibitor 2b; promoter regions (genetics); trans-activation (genetics); protein p16ink4a; humans; human; priority journal; article; protein p15; smad4 protein, human; cdkn2b protein, human; cdkn2b protein, mouse; zbtb17 protein, human; smad2 protein, human; smad2 protein, mouse; smad3 protein, mouse; smad4 protein, mouse; smad7 protein, human; smad7 protein, mouse |
| Journal Title: | Nature Cell Biology |
| Volume: | 3 |
| Issue: | 4 |
| ISSN: | 1465-7392 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2001-04-01 |
| Start Page: | 400 |
| End Page: | 408 |
| Language: | English |
| DOI: | 10.1038/35070086 |
| PUBMED: | 11283614 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 21 May 2015 -- Source: Scopus |
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