CTGF modulates cell cycle progression in cAMP-arrested NRK fibroblasts.
Connective tissue growth factor (CTGF) is a 38-kDa cysteine-rich peptide, whose synthesis and secretion are selectively induced by transforming growth factor beta (TGF-beta) in connective tissue cells. Previous studies have demonstrated that CTGF functions as a downstream mediator of TGF-beta mitogenic activity, where it controls cell cycle progression through late G1 and S-phase entry of NRK fibroblast suspension cultures. Here we report that CTGF induces this S-phase entry by upregulating cyclin A levels. The molecular mechanism for cyclin A induction appears to be via reduction of p27(Kip1) levels, which results in hyperphosphorylation of pRb and release of E2F, a known modulator of cyclin A gene transcription. These data indicate that CTGF acts as a mediator of TGF-beta-induced fibroblast proliferation in suspension cultures by regulating cdk activities.
Kothapalli
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Department of Cell Biology, University of Miami School of Medicine, Miami, Florida, USA.
Grotendorst
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GR
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects*; D018797:Cell Cycle Proteins; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D055513:Connective Tissue Growth Factor; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D019925:Cyclin A / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006133:Growth Substances / Q000494:pharmacology*; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D007668:Kidney / Q000166:cytology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008934:Mitogens / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000235:genetics; D051381:Rats; D016160:Retinoblastoma Protein / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000494:pharmacology; D025521:Tumor Suppressor Proteins; D015854:Up-Regulation / Q000187:drug effects
C526316:CCN2 protein, rat; C493962:Cdkn1b protein, rat; D018797:Cell Cycle Proteins; D019925:Cyclin A; D006133:Growth Substances; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; D008934:Mitogens; D016160:Retinoblastoma Protein; D016212:Transforming Growth Factor beta; D025521:Tumor Suppressor Proteins; D055513:Connective Tissue Growth Factor; D050760:Cyclin-Dependent Kinase Inhibitor p27; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000242:Cyclic AMP; D018844:Cyclin-Dependent Kinases