T. Crook et al., SENSITIVITY OF P53 LYSINE MUTANTS TO UBIQUITIN-DIRECTED DEGRADATION TARGETED BY HUMAN PAPILLOMAVIRUS E6, Virology, 217(1), 1996, pp. 285-292
The activity of the p53 tumor suppressor protein is regulated, at leas
t in part, through the stability of the protein. p53 degradation in no
rmal cells is controlled by ubiquitin-dependent proteolysis, and activ
ation of p53 following DNA damage is associated with an increase in th
e stability of the protein. The human papillomavirus-encoded E6 protei
n abrogates p53 function by targeting it for rapid degradation, also t
hrough the ubiquitin pathway. Although the p53 protein is ubiquitinate
d following interaction with E6, we show here that none of the lysine
residues within p53 are specifically required for E6-targeted degradat
ion. Mutation of lysine residues within the C-terminus of p53 resulted
in resistance to E6-mediated degradation in vitro, although the abili
ty of the two proteins to form a complex was not affected. The same mu
tant was efficiently targeted for degradation in cells, however, illus
trating a lack of correlation between the in vitro and the in vivo ass
ays. (C) 1996 Academic Press, Inc.