Journal
MOLECULAR AND CELLULAR BIOLOGY
Volume 26, Issue 8, Pages 3114-3123Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.26.8.3114-3123.2006
Keywords
-
Categories
Funding
- NCI NIH HHS [P30 CA008748] Funding Source: Medline
- NHLBI NIH HHS [K08 HL004478, K08 HL 04478] Funding Source: Medline
- NIDDK NIH HHS [DK 52208, R01 DK052208, R56 DK052208] Funding Source: Medline
- NIGMS NIH HHS [R01 GM052597, GM 52597] Funding Source: Medline
Ask authors/readers for more resources
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 alpha 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 G, phase of the cell cycle; we now show that MEF is a short-lived protein whose expression level also peaks during late G, 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 G(1)/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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available