title: Differential-effects of transforming growth-factor-Beta-1 on protein-levels of p21 waf and cdk-2 and on cdk-2 kinase-activity in human rd and ccl64 mink lung-cells.
abstract: Currently, the cyclin-dependent kinase inhibitor p21 WAF-1 is considered to be a crucial downstream effector in the p53-specific pathway of negative growth control in mammalian cells. Wild-type p53, but not mutant forms of this protein, transactivate the WAF-1 gene. We show a correlation between growth-inhibition and induction of WAF-1 protein expression following transforming growth factor-beta 1 (TGF-beta 1) treatment of two human tumour cell lines devoid of wild-type p53 protein and in SV40-transformed WI38 fibroblasts. Inversely, TGF-beta 1 treatment of normal WI38 fibroblasts stimulates their growth and represses WAF-1 protein synthesis. As the mink lung epithelial CCL64 cell line is frequently used in TGF-B studies we included it in this study: TGF-beta 1 growth-inhibition is accompanied by induction of WAF-1 synthesis concomitantly with a reduction of cdk2 synthesis and of its histone kinase activity. However in the human tumour line RD, TGF-beta 1 did not affect cdk-2 protein levels but did reduce its histone kinase activity.
authors.affiliation: CTR UNIV ORSAY,INST CURIE,CNRS,UMR 146,GROWTH FACTORS GRP,F-91405 ORSAY,FRANCE.
authors.forename: S
authors.initials: S
authors.lastname: Raynal
authors.forename: D
authors.initials: D
authors.lastname: Lawrence