Deregulation of p53-interacting protein 53bp2 by chemotherapy drugs or proteasomal inhibition may modulate chemotherapy-induced cell death

Kirtine Lee, Charles Lopez

    Research output: Contribution to journalArticle

    Abstract

    53BP2 is an ankyrin repeat and SH3 domain containing protein that interacts with tumor suppressor p53 and enhances p53 transactivation function. High expression of 53BP2 can impede cell cycle progression at G2M and induce apoptosis. Lower levels of 53BP2 sensitize cells to doxorubicin- but not taxol-induced cell death. We have previously shown that 53BP2 is upregulated after treatment of cells with LTV-irradiation and that antisense downregualtion of 53BP2 promotes survival after UV-irradiation. In the present study, we demonstrate that 53BP2 protein is also upregulated by some drugs used in cancer chemotherapy. Although both 53BP2 and p53 are upregulated by chemotherapy drugs, they are not upregulated concordantly. Doxorubicin and idarubicin upregulate both 53BP2 and p53, vinblastine upregulates p53 but not 53BP2, and L-asparaginase upregulates 53BP2 but not p53. Upregulation is more pronounced in p53 +/+ cells, which have a lower baseline level of 53BP2, compared to p53 -/- cells. 53BP2 mRNA is not upregulated by doxorubicin suggesting that increased levels of 53BP2 may be due to an increased rate of protein synthesis or stabilization of 53BP2 protein. Consistent with stabilization of 53BP2 is that treatment of HT 1080 cells with inhibitors of the proteasome but not other proteases results in increased 53BP2 protein but not mRNA. Since 53BP2 is upregulated by chemotherapy drugs and its expression can sensitize cells to chemotherapy drugs, 53BP2 may amplify the death-inducing effects of chemotherapy. Our results suggest that regulation of 53BP2 is complex and may play an important role in the cellular response to chemotherapy.

    Original languageEnglish (US)
    Pages (from-to)174b
    JournalBlood
    Volume96
    Issue number11 PART II
    StatePublished - Dec 1 2000

    ASJC Scopus subject areas

    • Biochemistry
    • Immunology
    • Hematology
    • Cell Biology

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