Cytoskeleton-interacting LIM-domain protein CRP1 suppresses cell proliferation and protects from stress-induced cell death.
Members of the cysteine-rich protein (CRP) family are actin cytoskeleton-interacting LIM-domain proteins known to act in muscle cell differentiation. We have earlier found that CRP1, a founding member of this family, is transcriptionally induced by UV radiation in human diploid fibroblasts [M. Gentile, L. Latonen, M. Laiho, Cell cycle arrest and apoptosis provoked by UV radiation-induced DNA damage are transcriptionally highly divergent responses, Nucleic Acids Res. 31 (2003) 4779-4790]. Here we show that CRP1 is induced by growth-inhibitory signals, such as increased cellular density, and cytotoxic stress induced by UV radiation or staurosporine. We found that high levels of CRP1 correlate with differentiation-associated morphology towards the myofibroblast lineage and that expression of ectopic CRP1 suppresses cell proliferation. Following UV- and staurosporine-induced stresses, expression of CRP1 provides a survival advantage evidenced by decreased cellular death and increased cellular metabolic activity and attachment. Our studies identify that CRP1 is a novel stress response factor, and provide evidence for its growth-inhibitory and cytoprotective functions.
Latonen
Leena
L
Molecular Cancer Biology Program, University of Helsinki, PO Box 63, FIN-00014 Helsinki, Finland.
Järvinen
Päivi M
PM
Laiho
Marikki
M
D002352:Carrier Proteins / Q000096:biosynthesis / Q000502:physiology*; D016923:Cell Death; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival; D006801:Humans; D060588:LIM Domain Proteins; D008840:Microfilament Proteins / Q000096:biosynthesis / Q000502:physiology*; D019311:Staurosporine / Q000494:pharmacology; D014466:Ultraviolet Rays
C486181:CRIP1 protein, human; D002352:Carrier Proteins; D060588:LIM Domain Proteins; D008840:Microfilament Proteins; D019311:Staurosporine