Abstract
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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alternative Splicing / genetics
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Basic Helix-Loop-Helix Transcription Factors
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Cell Cycle / genetics
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Cell Cycle / physiology
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Cell Line
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Cell Nucleus / chemistry
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Down-Regulation
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Gene Expression Regulation*
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Homeodomain Proteins / analysis
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism*
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Humans
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Nuclear Proteins / analysis
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Phosphorylation
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Proteasome Endopeptidase Complex / physiology
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Proteasome Inhibitors
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Protein Interaction Mapping
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Protein Structure, Tertiary
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RNA, Messenger / analysis
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RNA, Messenger / metabolism
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RNA-Binding Proteins
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Repressor Proteins / analysis
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Repressor Proteins / genetics
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Repressor Proteins / metabolism*
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Transcription, Genetic / genetics
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Transcription, Genetic / physiology
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Two-Hybrid System Techniques
Substances
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BHLHE40 protein, human
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Basic Helix-Loop-Helix Transcription Factors
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Homeodomain Proteins
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MCRS1 protein, human
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Nuclear Proteins
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Proteasome Inhibitors
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RNA, Messenger
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RNA-Binding Proteins
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Repressor Proteins
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Proteasome Endopeptidase Complex
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ATP dependent 26S protease