Modifications of p53 protein and accumulation of p21 and gadd45 mRNA in TGF-β1 growth inhibited cells

Yosef Landesman, Frank Bringold, Diane D. Milne, David W. Meek

    Research output: Contribution to journalArticlepeer-review

    30 Citations (Scopus)

    Abstract

    Transforming growth factory beta (TGF-beta) is a potent growth inhibitor of epithelial cells. One of the strategies used to elucidate the anti-proliferative mode of action of TGF-beta is to find out whether the receptor-generated signals interact with components of the basic machinery of the cell cycle. In this study we examined whether p53 and two other cycle inhibitory genes that can be transactivated by p53 are affected by TGF-beta 1 in epithelial cells. We show that TGF-beta 1 signalling controls the intracellular localization as well as the phosphorylation pattern and the stability of p53 protein. TGF-beta signalling also elevates the expression of p21/waf-1 and gadd45. The observed modifications in the protein suggest that p53 is involved in mediation of TGF-beta 1 growth inhibition. However, in TGF-beta 1 growth inhibited cells, wild type p53 is not required for the accumulation of the two p53 downstream targets p21/waf-1 and gadd45.
    Original languageEnglish
    Pages (from-to)291-298
    Number of pages8
    JournalCellular Signalling
    Volume9
    Issue number3-4
    DOIs
    Publication statusPublished - May 1997

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