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 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.
Chang
David F
DF
The Center for Cardiovascular Development, Baylor College of Medicine, Houston, TX 77030, USA.
Belaguli
Narasimhaswamy S
NS
Iyer
Dinakar
D
Roberts
Wilmer B
WB
Wu
San-Pin
SP
Dong
Xiu-Rong
XR
Marx
Joseph G
JG
Moore
Mary Shannon
MS
Beckerle
Mary C
MC
Majesky
Mark W
MW
Schwartz
Robert J
RJ
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D030161:Avian Proteins; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002319:Cardiovascular System / Q000166:cytology / Q000196:embryology; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002642:Chick Embryo; D004268:DNA-Binding Proteins / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D050981:Erythroid-Specific DNA-Binding Factors; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D060588:LIM Domain Proteins; D046911:Macromolecular Substances; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D026362:Serum Response Factor / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation
D048868:Adaptor Proteins, Signal Transducing; D030161:Avian Proteins; D022782:CCAAT-Enhancer-Binding Protein-beta; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D060588:LIM Domain Proteins; D046911:Macromolecular Substances; D012333:RNA, Messenger; D026362:Serum Response Factor; D014157:Transcription Factors