Journal
CELL CYCLE
Volume 6, Issue 13, Pages 1594-1604Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.6.13.4336
Keywords
cell cycle; transcription; repression; ets; corepressor; v-abl; MAP kinase
Categories
Funding
- NHLBI NIH HHS [R01 HL59694] Funding Source: Medline
- NIGMS NIH HHS [T32 GM08666] Funding Source: Medline
Ask authors/readers for more resources
The molecular mechanisms that control the proliferation and differentiation of specific cell types remain poorly understood. Positive ETS factors play important roles in mediating proliferative responses to Ras/ MAPK signaling in many cell types following mitogenic stimulation. PE- 1/ METS, a member of the ETS- domain family transcription factors that functions as a transcriptional repressor, can block mitogenic responses mediated by positively acting Ets factors. The anti- proliferative functions of PE- 1/ METS require its interaction with DP103, a multifunctional DEAD- box protein that mediates interactions with corepressor proteins and acts in a cooperative manner with Rb family members and to repress cell cycle control genes. ETS- 2 repressor factor ( ERF) is structur ally related to and also functions as a transcriptional repressor, but endogenous target genes and mechanisms of repression remain unknown. Here, we demonstrate that like PE- 1/ METS, ERF- mediated repression also requires DP103, and that ERF negatively regulates the c - myc and cdc2 genes. In contrast to PE- 1/ METS, however, ERF- mediated repression of these genes is inactivated by MAPK signaling through phosphorylation sites that are ERF- specific. Furthermore, constitutive activation of the Ras/ MAPK pathway in RAW 264.7 cells transformed by the v- Abelson leukemia virus is associated with constitutive inactivation of ERF in this cell type. We propose that ERF and PE- 1/ METS function to impose ` repression checkpoints' on a subset of cell cycle control genes that are differentially regulated by growth factor signaling pathways that control proliferation and differentiation and that ERF is targeted for inactivation by transforming oncogenes such as vAbl.
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