Accumulation of p53 in a mutant cell line defective in the ubiquitin pathway.
The wild-type p53 gene product plays an important role in the control of cell proliferation, differentiation, and survival. Altered function is frequently associated with changes in p53 stability. We have studied the role of the ubiquitination pathway in the degradation of p53, utilizing a temperature-sensitive mutant, ts20, derived from the mouse cell line BALB/c 3T3. We found that wild-type p53 accumulates markedly because of decreased breakdown when cells are shifted to the restrictive temperature. Introduction of sequences encoding the human ubiquitin-activating enzyme E1 corrects the temperature sensitivity defect in ts20 and prevents accumulation of p53. The data therefore strongly indicate that wild-type p53 is degraded intracellularly by the ubiquitin-mediated proteolytic pathway.
Chowdary
D R
DR
Department of Microbiology and Molecular Genetics, UMDNJ-New Jersey Medical School, Newark 07103.
Dermody
J J
JJ
Jha
K K
KK
Ozer
H L
HL
D016475:3T3 Cells; D000818:Animals; D066298:In Vitro Techniques; D008025:Ligases / Q000378:metabolism; D051379:Mice; D009154:Mutation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D044764:Ubiquitin-Activating Enzymes; D044767:Ubiquitin-Protein Ligases; D014452:Ubiquitins / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53; D014452:Ubiquitins; D044767:Ubiquitin-Protein Ligases; D008025:Ligases; D044764:Ubiquitin-Activating Enzymes