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J Cell Physiol. 2000 Jan;182(1):119-26.

CTGF modulates cell cycle progression in cAMP-arrested NRK fibroblasts.

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1
Department of Cell Biology, University of Miami School of Medicine, Miami, Florida, USA.

Abstract

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.

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