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The M dm Network and Its Regulation of p53 Activities: A Rheostat of Cancer Risk
Author(s) -
Eischen Christine M.,
Lozano Guillermina
Publication year - 2014
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22524
Subject(s) - biology , mdm2 , missense mutation , cancer research , mechanism (biology) , function (biology) , genetics , bioinformatics , mutation , microbiology and biotechnology , gene , philosophy , epistemology
The potent transcriptional activity of p53 ( T rp53, TP 53) must be kept in check for normal cell growth and survival. Tumors, which drastically deviate from these parameters, have evolved multiple mechanisms to inactivate TP 53, the most prevalent of which is the emergence of TP 53 missense mutations, some of which have gain‐of‐function activities. Another important mechanism by which tumors bypass TP 53 functions is via increased levels of two TP 53 inhibitors, MDM 2, and MDM 4. Studies in humans and in mice reveal the complexity of TP 53 regulation and the exquisite sensitivity of this pathway to small changes in regulation. Here, we summarize the factors that impinge on TP 53 activity and thus cell death/arrest or tumor development.