Repression of p15INK4b expression by Myc through association with Miz-1 Journal Article
| Authors: | Staller, P.; Peukert, K.; Kiermaier, A.; Seoane, J.; Lukas, J.; Karsunky, H.; Möröy, T.; Bartek, J.; Massagué, J.; Hänel, F.; Eilers, M. |
| Article Title: | Repression of p15INK4b expression by Myc through association with Miz-1 |
| Abstract: | Deregulated expression of c-myc can induce cell proliferation in established cell lines and in primary mouse embryonic fibroblasts (MEFs), through a combination of both transcriptional activation and repression by Myc. Here we show that a Myc-associated transcription factor, Miz-1, arrests cells in G1 phase and inhibits cyclin D-associated kinase activity. Miz-1 upregulates expression of the cyclin-dependent kinases (CDK) inhibitor p15INK4b by binding to the initiator element of the p15INK4b promoter. Myc and Max form a complex with Miz-1 at the p15 initiator and inhibit transcriptional activation by Miz-1. Expression of Myc in primary cells inhibits the accumulation of p15INK4b that is associated with cellular senescence; conversely, deletion of c-myc in an established cell line activates p15INK4b expression. Alleles of c-myc that are unable to bind to Miz-1 fail to inhibit accumulation of p15INK4b messenger RNA in primary cells and are, as a consequence, deficient in immortalization. |
| Keywords: | controlled study; protein expression; carrier protein; dna binding protein; human cell; promoter region; gene deletion; genetics; dna-binding proteins; cell cycle protein; mouse; animal; metabolism; animals; cell cycle proteins; mice; allele; complex formation; enzyme inhibition; gene expression; nuclear protein; cell line; protein binding; transcription factor; hela cell; hela cells; transcription factors; nuclear proteins; gene expression regulation; biosynthesis; hybrid protein; recombinant fusion proteins; messenger rna; myc protein; transactivator protein; carrier proteins; tumor suppressor proteins; rat; transactivation; rats; trans-activators; cyclin-dependent kinase inhibitor p16; tumor suppressor protein; cyclin dependent kinase; cyclin dependent kinase inhibitor; proto-oncogene proteins c-myc; zinc finger protein; oncogene c myb; cell cycle g1 phase; cell strain 3t3; 3t3 cells; zinc fingers; cyclin-dependent kinase inhibitor p15; cell immortalization; cyclin dependent kinase inhibitor 2b; promoter regions (genetics); protein p16ink4a; humans; human; priority journal; article; protein p15; cdkn2b protein, human; cdkn2b protein, mouse; cdkn2b protein, rat; zbtb17 protein, human |
| Journal Title: | Nature Cell Biology |
| Volume: | 3 |
| Issue: | 4 |
| ISSN: | 1465-7392 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2001-04-01 |
| Start Page: | 392 |
| End Page: | 399 |
| Language: | English |
| DOI: | 10.1038/35070076 |
| PUBMED: | 11283613 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 21 May 2015 -- Source: Scopus |
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