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2016 ; 6
(5
): ä Nephropedia Template TP
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Tumor-Suppressor Functions of the TP53 Pathway
#MMPMID27141080
Aubrey BJ
; Strasser A
; Kelly GL
Cold Spring Harb Perspect Med
2016[May]; 6
(5
): ä PMID27141080
show ga
The fundamental biological importance of the Tp53 gene family is highlighted by
its evolutionary conservation for more than one billion years dating back to the
earliest multicellular organisms. The TP53 protein provides essential functions
in the cellular response to diverse stresses and safeguards maintenance of
genomic integrity, and this is manifest in its critical role in tumor
suppression. The importance of Tp53 in tumor prevention is exemplified in human
cancer where it is the most frequently detected genetic alteration. This is
confirmed in animal models, in which a defective Tp53 gene leads inexorably to
cancer development, whereas reinstatement of TP53 function results in regression
of established tumors that had been initiated by loss of TP53. Remarkably,
despite extensive investigation, the specific mechanisms by which TP53 acts as a
tumor suppressor are yet to be fully defined. We review the history and current
standing of efforts to understand these mechanisms and how they complement each
other in tumor suppression.
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