Open Accessc-myc and bcl-2 modulate p53 function by altering p53 subcellular trafficking during the cell cycle.
Author(s) -
Jeanne Ryan,
Edward V. Prochownik,
C A Gottlieb,
Ingrid J. Apel,
Ramón Merino,
Gabriel Núñez,
Michael F. Clarke
Publication year - 1994
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.91.13.5878
Subject(s) - microbiology and biotechnology , cell cycle checkpoint , cell cycle , cytoplasm , biology , subcellular localization , haematopoiesis , function (biology) , apoptosis , cell growth , cancer research , stem cell , genetics
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.