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 transcription; in turn, p53 transcriptionally induces other proteins. Herein 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 expression of exogenous wt p53 induced p21WAF1/CIP1 but not p120, excluding p120 as a transcriptional target of p53. Like p53, induction of p120 by anticancer drugs did not require transcription. Induction of p120 by actinomycin-D occurred at concentrations which inhibit RNA synthesis and p120 mRNA levels. Inhibition of proteasomes resulted in accumulation of higher molecular weight proteins, reacting with anti-p120 antibodies. This suggests that the mechanisms of p120 and p53 induction are similar and involve inhibition of degradation. p120 protein stabilization represents an expedient means for accumulation of key response proteins following exposure to cytotoxic agents.
Blagosklonny
M V
MV
Medicine Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. mikhailb@box-m.nih.gov
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D000970:Antineoplastic Agents / Q000494:pharmacology*; D001483:Base Sequence; D002455:Cell Division; D004249:DNA Damage; D017931:DNA Primers / Q000235:genetics; D003609:Dactinomycin / Q000494:pharmacology; D003630:Daunorubicin / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D006801:Humans; D008870:Microtubules / Q000187:drug effects; D016685:Mitomycin / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D017239:Paclitaxel / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D014750:Vincristine / Q000494:pharmacology; D012359:tRNA Methyltransferases
D000970:Antineoplastic Agents; D017931:DNA Primers; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53; D003609:Dactinomycin; D016685:Mitomycin; D014750:Vincristine; D004317:Doxorubicin; C065028:NOP2 protein, human; D012359:tRNA Methyltransferases; D017239:Paclitaxel; D003630:Daunorubicin