c-myc and bcl-2 modulate p53 function by altering p53 subcellular trafficking during the cell cycle.
We have studied the ability of c-myc and bcl-2 oncogenes to modulate p53 function. Our studies show that coincident expression of human Bcl-2 protein with p53 prolongs survival of murine erythroleukemia cells. This effect was associated with a loss of the G1 specificity of p53-mediated cell cycle arrest. Furthermore, we found that the c-myc and bcl-2 genes cooperate to inhibit p53 functions. Coexpression of bcl-2 and c-myc can totally overcome p53-induced apoptosis and cell cycle arrest by altering the subcellular trafficking of p53 during the cell cycle: the p53 remains in the cytoplasm of the cotransfected cells during a critical period in G1. This finding suggests a mechanism by which normal hematopoietic progenitors can survive and proliferate despite p53 expression and by which the inappropriate expression of bcl-2 and c-myc can cooperate in transformation.
Department of Medicine, University of Michigan Medical Center, Ann Arbor 48109.
J J
JJ
Ryan
E
E
Prochownik
C A
CA
Gottlieb
I J
IJ
Apel
R
R
Merino
G
G
Nuñez
M F
MF
Clarke
D000818:Animals; D000911:Antibodies, Monoclonal; D002453:Cell Cycle; D002460:Cell Line; D002470:Cell Survival; D005434:Flow Cytometry; D016259:Genes, myc; D016158:Genes, p53; D006801:Humans; D051379:Mice; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis*; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000302:isolation & purification / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D011505:Protein-Tyrosine Kinases