Induction of bax by genotoxic stress in human cells correlates with normal p53 status and apoptosis.
DNA-damaging agents such as ionizing radiation (IR) activate the tumor suppressor p53 and in some cases can cause apoptosis. M1 cells, which do not express the endogenous tumor suppressor gene p53, undergo apoptosis following activation of a temperature sensitive p53 transgene, where it has been shown that bax, an important mediator of apoptosis, is a p53 target gene (Selvakumaran et al, Oncogene 9, 1791-8, 1994). Since p53 can function as a transcription factor after activation by IR, the genetic response to this stress was examined in a panel of human cells with defined p53 status. Like the p53-regulated gene gadd45, bax was rapidly induced, as measured by increased mRNA levels, in the p53 wt (wild type) human myeloid line ML-1, and it was not induced in cells lacking functional p53. However, unlike other p53-regulated genes, bax was only induced in p53 wt cells in which IR also triggered apoptosis. In the case of bcl2, which opposes bax function, mRNA levels were reduced in ML-1 cells after IR. Thus, bax appears to be an unique p53-regulated gene in that its induction by IR not only requires functional p53 but also requires that the cells be apoptosis "proficient."
Zhan
Q
Q
Laboratory of Molecular Pharmacology, National Cancer Institute, Bethesda, MD 20892.
Fan
S
S
Bae
I
I
Guillouf
C
C
Liebermann
D A
DA
O'Connor
P M
PM
Fornace
A J
AJ
D017209:Apoptosis / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics / Q000528:radiation effects; D016158:Genes, p53; D006801:Humans; D009153:Mutagens / Q000633:toxicity*; D009369:Neoplasms / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D009153:Mutagens; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein