RGD Reference Report - CHIP represses myocardin-induced smooth muscle cell differentiation via ubiquitin-mediated proteasomal degradation. - Rat Genome Database

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CHIP represses myocardin-induced smooth muscle cell differentiation via ubiquitin-mediated proteasomal degradation.

Authors: Xie, Ping  Fan, Yongna  Zhang, Hua  Zhang, Yuan  She, Mingpeng  Gu, Dongfeng  Patterson, Cam  Li, Huihua 
Citation: Xie P, etal., Mol Cell Biol. 2009 May;29(9):2398-408. doi: 10.1128/MCB.01737-08. Epub 2009 Feb 23.
RGD ID: 401901238
Pubmed: PMID:19237536   (View Abstract at PubMed)
PMCID: PMC2668377   (View Article at PubMed Central)
DOI: DOI:10.1128/MCB.01737-08   (Journal Full-text)

Myocardin, a coactivator of serum response factor (SRF), plays a critical role in the differentiation of vascular smooth muscle cells (SMCs). However, the molecular mechanisms regulating myocardin stability and activity are not well defined. Here we show that the E3 ligase C terminus of Hsc70-interacting protein (CHIP) represses myocardin-dependent SMC gene expression and transcriptional activity. CHIP interacts with and promotes myocardin ubiquitin-mediated degradation by the proteasome in vivo and in vitro. Furthermore, myocardin ubiquitination by CHIP requires its phosphorylation. Importantly, CHIP overexpression reduces the level of myocardin-dependent SMC contractile gene expression and diminishes arterial contractility ex vivo. These findings for the first time, to our knowledge, demonstrate that CHIP-promoted proteolysis of myocardin plays a key role in the physiological control of SMC phenotype and vessel tone, which may have an important implication for pathophysiological conditions such as atherosclerosis, hypertension, and Alzheimer's disease.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Stub1Ratnegative regulation of vascular associated smooth muscle contraction involved_inIMP PMID:19237536UniProt 
MyocdRatpositive regulation of transcription by RNA polymerase II involved_inIMP PMID:19237536UniProt 
Stub1Ratprotein ubiquitination involved_inIDA PMID:19237536UniProt 

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MyocdRatcytoplasm located_inIDA PMID:19237536UniProt 
Stub1Ratcytoplasm located_inIDA PMID:19237536UniProt 
MyocdRatnucleus located_inIDA PMID:19237536UniProt 
Stub1Ratnucleus located_inIDA PMID:19237536UniProt 

Molecular Function

  

Objects Annotated

Genes (Rattus norvegicus)
Hspa1a  (heat shock protein family A (Hsp70) member 1A)
Hspa1b  (heat shock protein family A (Hsp70) member 1B)
Myocd  (myocardin)
Stub1  (STIP1 homology and U-box containing protein 1)


Additional Information