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Biochimie. 2015 Nov;118:44-50. doi: 10.1016/j.biochi.2015.07.024. Epub 2015 Jul 27.

The stress protein TP53INP1 plays a tumor suppressive role by regulating metabolic homeostasis.

Author information

1
Inserm, U1068, CRCM, Marseille, F-13009, France; Institut Paoli-Calmettes, Marseille, F-13009, France; Aix-Marseille Université, UM 105, Marseille, F-13284, France; CNRS, UMR7258, CRCM, Marseille, F-13009, France.
2
Inserm, U1068, CRCM, Marseille, F-13009, France; Institut Paoli-Calmettes, Marseille, F-13009, France; Aix-Marseille Université, UM 105, Marseille, F-13284, France; CNRS, UMR7258, CRCM, Marseille, F-13009, France. Electronic address: alice.carrier@inserm.fr.

Abstract

In the recent years, we have provided evidence that Tumor Protein 53-Induced Nuclear Protein 1 (TP53INP1) is a key stress protein with antioxidant-associated tumor suppressive function. The TP53INP1 gene, which is highly conserved in mammals, is over-expressed during stress responses including inflammation. This gene encodes two protein isoforms with nuclear or cytoplasmic subcellular localization depending on the context. TP53INP1 contributes to stress responses, thus preventing stress-induced dysfunctions leading to pathologies such as cancer. Two major mechanisms by which TP53INP1 functions have been unveiled. First, in the nucleus, TP53INP1 was shown to regulate the transcriptional activity of p53 and p73 by direct interaction, and to mediate the antioxidant activity of p53. Second, independently of p53, TP53INP1 contributes to autophagy and more particularly mitophagy through direct interaction with molecular actors of autophagy. TP53INP1 is thus required for the homeostasis of the mitochondrial compartment, and is therefore involved in the regulation of energetic metabolism. Finally, the antioxidant function of TP53INP1 stems from the control of mitochondrial reactive oxygen species production. In conclusion, TP53INP1 is a multifaceted protein endowed with multiple functions, including metabolic regulation, as is its main functional partner p53.

KEYWORDS:

Autophagy; Cancer; Metabolism; Mitochondria; Oxidative stress; TP53INP1

PMID:
26225460
DOI:
10.1016/j.biochi.2015.07.024
[Indexed for MEDLINE]

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