LIKE P53, THE PROLIFERATION-ASSOCIATED PROTEIN P120 ACCUMULATES IN HUMAN CANCER-CELLS FOLLOWING EXPOSURE TO ANTICANCER DRUGS

Accumulation of p53 protein following DNA damage is independent of tra nscription; in turn, p53 transcriptionally induces other proteins, Her ein we demonstrated that p120, a proliferation-associated protein, was induced by DNA-damaging and microtubule-active drugs in human cancer cells, However, induction of p120 was independent of p53; and expressi on of exogenous wt p53 induced p21(WAF1/CIP1) ut not p120, excluding p 120 as a transcriptional target of p53, Like p53, induction of p120 by anticancer drugs did not require transcription, Induction of p120 by actinomycin-D occured at concentrations which inhibit RNA synthesis an d p120 mRNA levels, Inhibition of proteasomes resulted in accumulation of higher molecular weight proteins, reacting with anti-p120 antibodi es, This suggests that the mechanisms of p120 and p53 induction are si milar and involve inhibition of degradation, p120 protein stabilizatio n represents an expedient means for accumulation of key response prote ins following exposure to cytotoxic agents. (C) 1998 Academic Press.