Back to Search
Start Over
The Corepressor mSin3A Regulates Phosphorylation-Induced Activation, Intranuclear Location, and Stability of AML1
- Source :
- Molecular and Cellular Biology. 24:1033-1043
- Publication Year :
- 2004
- Publisher :
- Informa UK Limited, 2004.
-
Abstract
- The AML1 (RUNX1) gene, one of the most frequent targets of translocations associated with human leukemias, encodes a DNA-binding protein that plays pivotal roles in myeloid differentiation through transcriptional regulation of various genes. Previously, we reported that AML1 is phosphorylated on two serine residues with dependence on activation of extracellular signal-regulated kinase, which positively regulates the transcriptional activity of AML1. Here, we demonstrate that the interaction between AML1 and the corepressor mSin3A is regulated by phosphorylation of AML1 and that release of AML1 from mSin3A induced by phosphorylation activates its transcriptional activity. Furthermore, phosphorylation of AML1 regulates its intranuclear location and disrupts colocalization of AML1 with mSin3A in the nuclear matrix. PEBP2 beta/CBF beta, a heterodimeric partner of AML1, was shown to play a role in protecting AML1 from proteasome-mediated degradation. We show that mSin3A also protects AML1 from proteasome-mediated degradation and that phosphorylation-induced release of AML1 from mSin3A results in degradation of AML1 in a time-dependent manner. This study provides a novel regulatory mechanism for the function of transcription factors mediated by protein modification and interaction with cofactors.
- Subjects :
- Transcription, Genetic
Repressor
Biology
DNA-binding protein
Histone Deacetylases
chemistry.chemical_compound
Proto-Oncogene Proteins
hemic and lymphatic diseases
Transcriptional regulation
Animals
Phosphorylation
neoplasms
Molecular Biology
Transcription factor
Cell Nucleus
Transcriptional Regulation
Epidermal Growth Factor
Kinase
Cell Biology
Fibroblasts
Molecular biology
Cell biology
DNA-Binding Proteins
Histone Deacetylase Inhibitors
Repressor Proteins
Sin3 Histone Deacetylase and Corepressor Complex
RUNX1
chemistry
COS Cells
Core Binding Factor Alpha 2 Subunit
Mutation
Mitogen-Activated Protein Kinases
Corepressor
Transcription Factors
Subjects
Details
- ISSN :
- 10985549
- Volume :
- 24
- Database :
- OpenAIRE
- Journal :
- Molecular and Cellular Biology
- Accession number :
- edsair.doi.dedup.....38e225bf25231e45dee11c76f86861a8