RT Journal Article
SR Electronic
T1 mdmx Is a Negative Regulator of p53 Activity <strong><em>in Vivo</em></strong>
JF Cancer Research
JO Cancer Res
FD American Association for Cancer Research
SP 3221
OP 3225
VO 62
IS 11
A1 Finch, Rick A.
A1 Donoviel, Dorit B.
A1 Potter, David
A1 Shi, Min
A1 Fan, Amy
A1 Freed, Deon D.
A1 Wang, Ching-yun
A1 Zambrowicz, Brian P.
A1 Ramirez-Solis, Ramiro
A1 Sands, Arthur T.
A1 Zhang, Nan
YR 2002
UL http://cancerres.aacrjournals.org/content/62/11/3221.abstract
AB Regulation of p53 protein activity is required for normal embryogenesis, tumor suppression, and cellular response to DNA damage. Here we report that loss of mdmx, a p53-binding protein, results in midgestational embryo lethality, a phenotype that is completely rescued by the absence of p53. Mice homozygous for both mdmx and p53 null mutations are viable and appear developmentally normal. Fibroblasts derived from embryos with reduced mdmx expression demonstrate a decreased growth rate and increased UV-induced apoptosis compared with wild-type cells and contain elevated levels of p53 and several p53 target proteins including the proapoptotic bax protein. These observations demonstrate that mdmx functions as a critical negative regulator of p53 in vivo.