Cyclin-dependent kinase antagonizes promyelocytic leukemia zinc-finger through phosphorylation Journal Article
| Authors: | Costoya, J. A.; Hobbs, R. M.; Pandolfi, P. P. |
| Article Title: | Cyclin-dependent kinase antagonizes promyelocytic leukemia zinc-finger through phosphorylation |
| Abstract: | Acute promyelocytic leukemia is associated with chromosomal translocations that involve the RARα gene and several distinct loci producing a variety of fusion proteins. One such fusion partner is promyelocytic leukemia zinc-finger gene (PLZF), a member of the POK (POZ and Krüppel) family of transcriptional repressors that is a key developmental regulator, stem cell maintenance factor and tumor suppressor. Overexpression of PLZF has been shown to induce cell cycle arrest at the G1 to S transition and repress the expression of key pro-proliferative genes such as CCNA2 and MYC. However, given this data suggesting an important growth inhibitory role for PLZF, relatively little is known regarding regulation of its activity. Here we show that the main cyclin-dependent kinase involved at the G1 to S transition (CDK2) phosphorylates PLZF at two consensus sites found within PEST domains present in the hinge region of the protein. This phosphorylation triggers the ubiquitination and subsequent degradation of PLZF, which impairs PLZF transcriptional repression ability and antagonizes its growth inhibitory effects. This critical mechanism of PLZF regulation may thus be relevant for cell cycle progression during the development and the pathogenesis of human cancer. © 2008 Nature Publishing Group All rights reserved. |
| Keywords: | controlled study; protein phosphorylation; human cell; nonhuman; protein domain; protein function; animal cell; animals; mice; gene; cell cycle; cell cycle progression; cell cycle s phase; protein degradation; transfection; cercopithecus aethiops; cos cells; phosphorylation; leukemia, promyelocytic, acute; ubiquitination; tumor necrosis factor-alpha; kruppel-like transcription factors; translocation, genetic; cyclin-dependent kinases; keratinocytes; repressor proteins; cell cycle g1 phase; cyclin dependent kinase 2; zinc fingers; transcriptional repression; pest domains; poz and krüppel-type zinc finger domains; promyelocytic leukemia zinc finger gene; haplorhini |
| Journal Title: | Oncogene |
| Volume: | 27 |
| Issue: | 27 |
| ISSN: | 0950-9232 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2008-06-19 |
| Start Page: | 3789 |
| End Page: | 3796 |
| Language: | English |
| DOI: | 10.1038/onc.2008.7 |
| PUBMED: | 18246121 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 8" - "Export Date: 17 November 2011" - "CODEN: ONCNE" - "Source: Scopus" |
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