Inhibition of RhoA-mediated SRF activation by p116Rip.
p116Rip, originally identified as a binding partner of activated RhoA, is an actin-binding protein that interacts with the regulatory myosin-binding subunit (MBS) of myosin-II phosphatase and is essential for Rho-regulated cytoskeletal contractility. Here, we have examined the role of p116Rip in RhoA-mediated activation of the transcription factor SRF. We show that p116Rip oligomerizes via its C-terminal coiled-coil domain and, when overexpressed, inhibits RhoA-induced SRF activation without affecting RhoA-GTP levels. Mutant forms of p116Rip that fail to oligomerize or bind to MBS are still capable of inhibiting SRF activity. Our results suggest that p116Rip interferes with RhoA-mediated transcription through its ability to disassemble the actomyosin cytoskeleton downstream of RhoA.
Mulder
Jacqueline
J
Division of Cellular Biochemistry and Centre for Biomedical Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Ariaens
Aafke
A
van Horck
Francis P G
FP
Moolenaar
Wouter H
WH
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D009154:Mutation; D018994:Myosin Light Chains / Q000378:metabolism; D017434:Protein Structure, Tertiary; D027602:Serum Response Element / Q000235:genetics; D026362:Serum Response Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014158:Transcription, Genetic; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism
D008840:Microfilament Proteins; D018994:Myosin Light Chains; D026362:Serum Response Factor; C500243:p116Rip protein, mouse; D020742:rhoA GTP-Binding Protein