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Miyashita, T, Krajewski, S, Krajewska, M, Wang, HG, Lin, HK, Liebermann, DA, Hoffman, B and Reed, JC (1994) Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo. Oncogene 9:1799-805
The p53 tumor suppressor gene product can induce apoptotic cell death through an unknown mechanism. Here we demonstrate that a temperature-sensitive p53 induces temperature-dependent decreases in the expression of the apoptosis-suppressing gene bcl-2 in the murine leukemia cell M1, while simultaneously stimulating increases in the expression of bax, a gene which encodes a dominant-inhibitor of the Bcl-2 protein. Mice deficient in p53 exhibit increases in Bcl-2 and decreases in Bax protein levels in several tissues as determined by immunohistochemical and immunoblot methods. The findings suggest a potential mechanism by which p53 regulates apoptosis, as well as responses to radiation and chemotherapeutic drugs in cancer.
Animals; Apoptosis; Base Sequence; Gene Expression Regulation; Genes, p53/physiology; Humans; Leukemia, Myeloid, Acute/metabolism; Leukemia, Myeloid, Acute/pathology; Mice; Molecular Sequence Data; Proto-Oncogene Proteins/analysis; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins c-bcl-2; Proto-Oncogenes; Rabbits; Temperature; Tumor Cells, Cultured; bcl-2-Associated X Protein
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