| Regulation of myocardin factor protein stability by the LIM-only protein FHL2. | |
| | |
MedLine Citation:
|
PMID: 18586895 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Extensive evidence indicates that serum response factor (SRF) regulates muscle-specific gene expression and that myocardin family SRF cofactors are critical for smooth muscle cell differentiation. In a yeast two hybrid screen for novel SRF binding partners expressed in aortic SMC, we identified four and a half LIM domain protein 2 (FHL2) and confirmed this interaction by GST pull-down and coimmunoprecipitation assays. FHL2 also interacted with all three myocardin factors and enhanced myocardin and myocardin-related transcription factor (MRTF)-A-dependent transactivation of smooth muscle alpha-actin, SM22, and cardiac atrial natriuretic factor promoters in 10T1/2 cells. The expression of FHL2 increased myocardin and MRTF-A protein levels, and, importantly, this effect was due to an increase in protein stability not due to an increase in myocardin factor mRNA expression. Treatment of cells with proteasome inhibitors MG-132 and lactacystin strongly upregulated endogenous MRTF-A protein levels and resulted in a substantial increase in ubiquitin immunoreactivity in MRTF-A immunoprecipitants. Interestingly, the expression of FHL2 attenuated the effects of RhoA and MRTF-B on promoter activity, perhaps through decreased MRTF-B nuclear localization or decreased SRF-CArG binding. Taken together, these data indicate that myocardin factors are regulated by proteasome-mediated degradation and that FHL2 regulates SRF-dependent transcription by multiple mechanisms, including stabilization of myocardin and MRTF-A. |
| | |
Authors:
|
Jeremiah S Hinson; Matt D Medlin; Joan M Taylor; Christopher P Mack |
Related Documents
:
|
7838525 - Direct relationship between the expression of tumor suppressor h19 mrna and c-mos proto... 21124855 - Molecular and functional characterization of hv1 proton channel in human granulocytes. 1875785 - Reduced levels of mrna for myofibrillar proteins in skeletal muscle from septic rats. 17285445 - Rna interference targeting embryonic myosin heavy chain isoform inhibited mrna expressi... 21694865 - Immunohistochemical localization of transforming growth factor β-1 and its relationshi... 9780025 - Transcriptional suppression of estrogen receptor gene expression by 2,3,7,8-tetrachloro... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural Date: 2008-06-27 |
Journal Detail:
|
Title: American journal of physiology. Heart and circulatory physiology Volume: 295 ISSN: 0363-6135 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2008 Sep |
Date Detail:
|
Created Date: 2008-09-08 Completed Date: 2008-10-16 Revised Date: 2009-11-18 |
Medline Journal Info:
|
Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
|
Languages: eng Pagination: H1067-H1075 Citation Subset: IM |
Affiliation:
|
Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599-7525, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Cells, Cultured Electrophoretic Mobility Shift Assay Genes, Reporter / genetics Glutathione Transferase / metabolism Homeodomain Proteins / genetics*, physiology* Muscle Proteins / genetics*, physiology* Nuclear Proteins / biosynthesis*, genetics* Plasmids / genetics Proteasome Endopeptidase Complex / genetics RNA / biosynthesis, genetics Rats Reverse Transcriptase Polymerase Chain Reaction Serum Response Factor / metabolism Subcellular Fractions / metabolism Trans-Activators / biosynthesis*, genetics* Transcription Factors / genetics*, physiology* Transcription, Genetic / genetics, physiology Transcriptional Activation / genetics, physiology Transfection Ubiquitin / genetics, physiology |
| Grant Support | |
ID/Acronym/Agency:
|
HL-070953/HL/NHLBI NIH HHS; HL-071054/HL/NHLBI NIH HHS; HL-081844/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Fhl2 protein, rat; 0/Homeodomain Proteins; 0/Muscle Proteins; 0/Nuclear Proteins; 0/Serum Response Factor; 0/Trans-Activators; 0/Transcription Factors; 0/Ubiquitin; 0/myocardin; 63231-63-0/RNA; EC 2.5.1.18/Glutathione Transferase; EC 3.4.25.1/Proteasome Endopeptidase Complex |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Molecular and physiological characterization of RV remodeling in a murine model of pulmonary stenosi...
Next Document: The acute effect of atrioventricular pacing on sympathetic nerve activity in patients with normal an...