The ETS protein MEF is regulated by phosphorylation-dependent proteolysis via the protein-ubiquitin ligase SCFSkp2 Journal Article
| Authors: | Liu, Y.; Hedvat, C. V.; Mao, S.; Zhu, X. H.; Yao, J.; Nguyen, H.; Koff, A.; Nimer, S. D. |
| Article Title: | The ETS protein MEF is regulated by phosphorylation-dependent proteolysis via the protein-ubiquitin ligase SCFSkp2 |
| Abstract: | MEF is an ETS-related transcription factor with strong transcriptional activating activity that affects hematopoietic stem cell behavior and is required for normal NK cell and NK T-cell development. The MEF (also known as ELF4) gene is repressed by several leukemia-associated fusion transcription factor proteins (PML-retinoic acid receptor α and AML1-ETO), but it is also activated by retroviral insertion in several cancer models. We have previously shown that cyclin A-dependent phosphorylation of MEF largely restricts its activity to the G1 phase of the cell cycle; we now show that MEF is a short-lived protein whose expression level also peaks during late G1 phase. Mutagenesis studies show that the rapid turnover of MEF in S phase is dependent on the specific phosphorylation of threonine 643 and serine 648 at the C terminus of MEF by cdk2 and on the Skp1/Cul1/F-box (SCF) E3 ubiquitin ligase complex SCFSkp2, which targets MEF for ubiquitination and proteolysis. Overexpression of MEF drives cells through the G1/S transition, thereby promoting cell proliferation. The tight regulation of MEF levels during the cell cycle contributes to its effects on regulating cell cycle entry and cell proliferation. Copyright © 2006, American Society for Microbiology. All Rights Reserved. |
| Keywords: | controlled study; protein phosphorylation; unclassified drug; human cell; dna-binding proteins; ubiquitin; cell proliferation; t lymphocyte; proteins; gene; cell cycle s phase; gene overexpression; serine; ubiquitin protein ligase; protein degradation; protein protein interaction; cell line; transcription factor; cell line, tumor; cysteine proteinase inhibitors; phosphorylation; transcription factors; gene expression regulation; ubiquitination; amino acid sequence; hybrid protein; natural killer cell; mutagenesis, site-directed; threonine; hematopoietic stem cell; cyclin a; hydrolysis; cell cycle g1 phase; half-life; s phase kinase associated protein 2; transcription factor ets; ligases; protein eto; transcription factor runx1; promyelocytic leukemia protein; retinoic acid receptor alpha; cyclin dependent kinase 2; leupeptins; transcription factor mef; mef gene |
| Journal Title: | Molecular and Cellular Biology |
| Volume: | 26 |
| Issue: | 8 |
| ISSN: | 0270-7306 |
| Publisher: | American Society for Microbiology |
| Date Published: | 2006-04-01 |
| Start Page: | 3114 |
| End Page: | 3123 |
| Language: | English |
| DOI: | 10.1128/mcb.26.8.3114-3123.2006 |
| PUBMED: | 16581786 |
| PROVIDER: | scopus |
| PMCID: | PMC1446966 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 19" - "Export Date: 4 June 2012" - "CODEN: MCEBD" - "Source: Scopus" |
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