p53-mediated cell death: relationship to cell cycle control.
M1 clone S6 myeloid leukemic cells do not express detectable p53 protein. When stably transfected with a temperature-sensitive mutant of p53, these cells undergo rapid cell death upon induction of wild-type (wt) p53 activity at the permissive temperature. This process has features of apoptosis. In a number of other cell systems, wt p53 activation has been shown to induce a growth arrest. Yet, wt 53 fails to induce a measurable growth arrest in M1 cells, and cell cycle progression proceeds while viability is being lost. There exists, however, a relationship between the cell cycle and p53-mediated death, and cells in G1 appear to be preferentially susceptible to the death-inducing activity of wt p53. In addition, p53-mediated M1 cell death can be inhibited by interleukin-6. The effect of the cytokine is specific to p53-mediated death, since apoptosis elicited by serum deprivation is refractory to interleukin-6. Our data imply that p53-mediated cell death is not dependent on the induction of a growth arrest but rather may result from mutually incompatible growth-regulatory signals.
Yonish-Rouach
E
E
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
Grunwald
D
D
Wilder
S
S
Kimchi
A
A
May
E
E
Lawrence
J J
JJ
May
P
P
Oren
M
M
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002453:Cell Cycle / Q000502:physiology*; D002455:Cell Division; D002470:Cell Survival; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D016193:G1 Phase / Q000502:physiology; D016259:Genes, myc; D015850:Interleukin-6 / Q000494:pharmacology; D007951:Leukemia, Myeloid / Q000235:genetics / Q000503:physiopathology*; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
D016895:Culture Media, Serum-Free; D015850:Interleukin-6; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D016159:Tumor Suppressor Protein p53