Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo.
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.
Miyashita
T
T
La Jolla Cancer Research Foundation, Cancer Research Center, CA 92037.
Krajewski
S
S
Krajewska
M
M
Wang
H G
HG
Lin
H K
HK
Liebermann
D A
DA
Hoffman
B
B
Reed
J C
JC
D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D005786:Gene Expression Regulation; D016158:Genes, p53 / Q000502:physiology*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D011519:Proto-Oncogenes; D011817:Rabbits; D013696:Temperature; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; C494827:Bax protein, mouse; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein