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Int J Mol Sci. 2016 Dec 6;17(12). pii: E2041.

The Regulation of Tumor Suppressor p63 by the Ubiquitin-Proteasome System.

Author information

1
370 Heritage Medical Research Center, Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB T6G 2S2, Canada. ar2@ualberta.ca.
2
370 Heritage Medical Research Center, Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB T6G 2S2, Canada. hwu8@ualberta.ca.
3
370 Heritage Medical Research Center, Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB T6G 2S2, Canada. benfan@ualberta.ca.
4
370 Heritage Medical Research Center, Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB T6G 2S2, Canada. abuetabh@ualberta.ca.
5
Department of Laboratory Medicine and Pathology (5B4. 09), University of Alberta, Edmonton, AB T6G 2B7, Canada. sergi@ualberta.ca.
6
370 Heritage Medical Research Center, Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB T6G 2S2, Canada. rleng@ualberta.ca.

Abstract

The protein p63 has been identified as a homolog of the tumor suppressor protein p53 and is capable of inducing apoptosis, cell cycle arrest, or senescence. p63 has at least six isoforms, which can be divided into two major groups: the TAp63 variants that contain the N-terminal transactivation domain and the ΔNp63 variants that lack the N-terminal transactivation domain. The TAp63 variants are generally considered to be tumor suppressors involved in activating apoptosis and suppressing metastasis. ΔNp63 variants cannot induce apoptosis but can act as dominant negative inhibitors to block the function of TAp53, TAp73, and TAp63. p63 is rarely mutated in human tumors and is predominately regulated at the post-translational level by phosphorylation and ubiquitination. This review focuses primarily on regulation of p63 by the ubiquitin E-3 ligase family of enzymes via ubiquitination and proteasome-mediated degradation, and introduces a new key regulator of the p63 protein.

KEYWORDS:

AIP 4; E3 ligases; Mdm2; Mdm4; WWP1; degradation; p63; ubiquitination

PMID:
27929429
PMCID:
PMC5187841
DOI:
10.3390/ijms17122041
[Indexed for MEDLINE]
Free PMC Article

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