Cysteine-Rich LIM-Only Proteins CRP1 and CRP2 Are Potent Smooth Muscle Differentiation Cofactors

Cysteine-rich LIM-only proteins, CRP1 and CRP2, expressed during cardiovascular development act as bridging molecules that associate with serum response factor and GATA proteins. SRF-CRP-GATA complexes strongly activated smooth muscle gene targets. CRP2 was found in the nucleus during early stages o...

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Bibliographic Details
Published in:Developmental cell 2003, Vol.4 (1), p.107-118
Main Authors: Chang, David F., Belaguli, Narasimhaswamy S., Iyer, Dinakar, Roberts, Wilmer B., Wu, San-Pin, Dong, Xiu-Rong, Marx, Joseph G., Moore, Mary Shannon, Beckerle, Mary C., Majesky, Mark W., Schwartz, Robert J.
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing
Animals
Avian Proteins
Cardiovascular System - cytology
Cardiovascular System - embryology
Carrier Proteins - chemistry
Carrier Proteins - genetics
Carrier Proteins - metabolism
CCAAT-Enhancer-Binding Protein-beta - chemistry
CCAAT-Enhancer-Binding Protein-beta - genetics
CCAAT-Enhancer-Binding Protein-beta - metabolism
Cell Differentiation
Chick Embryo
DNA-Binding Proteins - metabolism
Electrophoretic Mobility Shift Assay
Erythroid-Specific DNA-Binding Factors
Gene Expression Regulation, Developmental
In Situ Hybridization
LIM Domain Proteins
Macromolecular Substances
Muscle, Smooth, Vascular - cytology
Muscle, Smooth, Vascular - metabolism
Promoter Regions, Genetic - genetics
Protein Binding
RNA, Messenger - genetics
RNA, Messenger - metabolism
Serum Response Factor - metabolism
Transcription Factors - metabolism
Transcriptional Activation
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Summary:Cysteine-rich LIM-only proteins, CRP1 and CRP2, expressed during cardiovascular development act as bridging molecules that associate with serum response factor and GATA proteins. SRF-CRP-GATA complexes strongly activated smooth muscle gene targets. CRP2 was found in the nucleus during early stages of coronary smooth muscle differentiation from proepicardial cells. A dominant-negative CRP2 mutant blocked proepicardial cells from differentiating into smooth muscle cells. Together with SRF and GATA proteins, CRP1 and CRP2 converted pluripotent 10T1/2 fibroblasts into smooth muscle cells, while muscle LIM protein CRP3 inhibited the conversion. Thus, LIM-only proteins of the CRP family play important roles in organizing multiprotein complexes, both in the cytoplasm, where they participate in cytoskeletal remodeling, and in the nucleus, where they strongly facilitate smooth muscle differentiation.
ISSN:1534-5807
1878-1551
DOI:10.1016/S1534-5807(02)00396-9