Dr. Chowdary et al., ACCUMULATION OF P53 IN A MUTANT-CELL LINE DEFECTIVE IN THE UBIQUITIN PATHWAY, Molecular and cellular biology, 14(3), 1994, pp. 1997-2003
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 studi
ed the role of the ubiquitination pathway in the degradation of p53, u
tilizing 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 restrict
ive temperature. Introduction of sequences encoding the human ubiquiti
n-activating enzyme El corrects the temperature sensitivity defect in
ts20 and prevents accumulation of p53. The data therefore strongly ind
icate that wild-type p53 is degraded intracellularly by the ubiquitin-
mediated proteolytic pathway.