Regulation of Mutant p53 Protein Expression
AuthorVijayakumaran, R; Tan, KH; Miranda, PJ; Haupt, S; Haupt, Y
Source TitleFrontiers in Oncology
PublisherFRONTIERS MEDIA SA
AffiliationSir Peter MacCallum Department of Oncology
Document TypeJournal Article
CitationsVijayakumaran, R., Tan, K. H., Miranda, P. J., Haupt, S. & Haupt, Y. (2015). Regulation of Mutant p53 Protein Expression. FRONTIERS IN ONCOLOGY, 5 (DEC), https://doi.org/10.3389/fonc.2015.00284.
Access StatusOpen Access
For several decades, p53 has been detected in cancer biopsies by virtue of its high protein expression level which is considered indicative of mutation. Surprisingly, however, mouse genetic studies revealed that mutant p53 is inherently labile, similar to its wild type (wt) counterpart. Consistently, in response to stress conditions, both wt and mutant p53 accumulate in cells. While wt p53 returns to basal level following recovery from stress, mutant p53 remains stable. In part, this can be explained in mutant p53-expressing cells by the lack of an auto-regulatory loop with Mdm2 and other negative regulators, which are pivotal for wt p53 regulation. Further, additional protective mechanisms are acquired by mutant p53, largely mediated by the co-chaperones and their paralogs, the stress-induced heat shock proteins. Consequently, mutant p53 is accumulated in cancer cells in response to chronic stress and this accumulation is critical for its oncogenic gain of functions (GOF). Building on the extensive knowledge regarding wt p53, the regulation of mutant p53 is unraveling. In this review, we describe the current understanding on the major levels at which mutant p53 is regulated. These include the regulation of p53 protein levels by microRNA and by enzymes controlling p53 proteasomal degradation.
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