TY - JOUR
T1 - Structural and functional analysis of p53
T2 - The acidic activation domain has transforming capability
AU - Hulboy, D. L.
AU - Lozano, G.
PY - 1994
Y1 - 1994
N2 - The p53 gene encodes a transcriptional activator that is able to suppress transformation. The protein can be divided into three functional domains: the acidic activation domain at the amino terminus; the oligomerization and nonspecific DNA binding regions in the carboxyl terminus; and the conformation domain, responsible for specific DNA binding, in the middle. To further examine the structural/functional relationship of p53, we undertook a functional study of deletion mutants of the protein. We assayed these mutants for their abilities to activate transcription, transform rat embryo fibroblasts, and oligomerize. Analysis of the results indicates that: (a) besides specific DNA binding, an intact conformation domain is necessary for the transactivation and oligomerization functions of p53; and (b) p53 mutants that contain the amino and carboxyl termini do not oligomerize with wild- type p53, yet they transform cells. In fact, the amino terminus alone transforms rat embryo fibroblasts. Transformation by these mutants is probably effected by the amino terminus binding and sequestration of factors essential for wild-type p53 function.
AB - The p53 gene encodes a transcriptional activator that is able to suppress transformation. The protein can be divided into three functional domains: the acidic activation domain at the amino terminus; the oligomerization and nonspecific DNA binding regions in the carboxyl terminus; and the conformation domain, responsible for specific DNA binding, in the middle. To further examine the structural/functional relationship of p53, we undertook a functional study of deletion mutants of the protein. We assayed these mutants for their abilities to activate transcription, transform rat embryo fibroblasts, and oligomerize. Analysis of the results indicates that: (a) besides specific DNA binding, an intact conformation domain is necessary for the transactivation and oligomerization functions of p53; and (b) p53 mutants that contain the amino and carboxyl termini do not oligomerize with wild- type p53, yet they transform cells. In fact, the amino terminus alone transforms rat embryo fibroblasts. Transformation by these mutants is probably effected by the amino terminus binding and sequestration of factors essential for wild-type p53 function.
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M3 - Article
C2 - 7848903
AN - SCOPUS:0028051398
SN - 1044-9523
VL - 5
SP - 1023
EP - 1031
JO - Cell Growth and Differentiation
JF - Cell Growth and Differentiation
IS - 10
ER -