Association, mutual stabilization, and transcriptional activity of the STRA13 and MSP58 proteins.
STRA13 is a hypoxia-inducible bHLH transcription factor implicated in the pVHL/HIF, TGF-beta, and Jak/STAT pathways. To further characterize the STRA13 protein-interacting network and mechanisms of STRA13-dependent transcription, we utilized yeast two-hybrid screening. Here we report on STRA13 interaction with the cell cycle-associated transcription factor MSP58. We demonstrated that the basic domain of STRA13 and the FHA domain of MSP58 are essential for this association. We performed phospho-peptide mapping of both MSP58 and STRA13 and showed that their association was modulated by the STRA13 phosphorylation status. STRA13/MSP58 complex formation protected both proteins from the proteasome-mediated degradation, extending their half-lives considerably. STRA13 and MSP58 synergistically co-operated in the STRA13 promoter-driven transcription repression. Both proteins were co-localized in the nucleus and showed transcript accumulation during the S phase of the cell cycle. Thus, we characterize a novel STRA13-associated transcription repression complex and provide a link between cell cycle regulation and STRA13 activity.
Ivanova
A V
AV
Laboratory of Immunobiology, Basic Research Program, SAIC-Frederick Inc., NCI-Frederick, MD 21702, USA. ivanova@mail.ncifcrf.gov
Ivanov
S V
SV
Lerman
M L
ML
D017398:Alternative Splicing / Q000235:genetics; D051792:Basic Helix-Loop-Helix Proteins; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry; D015536:Down-Regulation; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000502:physiology; D061988:Proteasome Inhibitors; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D016601:RNA-Binding Proteins; D012097:Repressor Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics / Q000502:physiology; D020798:Two-Hybrid System Techniques
D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D046988:Proteasome Endopeptidase Complex; D061988:Proteasome Inhibitors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; C107989:BHLHE40 protein, human; C113292:MCRS1 protein, human; C061553:ATP dependent 26S protease
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