Absence of Tumor Suppressor Tumor Protein 53-Induced Nuclear Protein 1 (TP53INP1) Sensitizes Mouse Thymocytes and Embryonic Fibroblasts to Redox-Driven Apoptosis - Archive ouverte HAL Access content directly
Journal Articles Antioxidants and Redox Signaling Year : 2011

Absence of Tumor Suppressor Tumor Protein 53-Induced Nuclear Protein 1 (TP53INP1) Sensitizes Mouse Thymocytes and Embryonic Fibroblasts to Redox-Driven Apoptosis

(1) , (1) , (2, 1) , (1) , (1) , (1) , (1) , (2) , (2) , (2) , , (2) , (1)
1
2

Abstract

The p53-transcriptional target TP53INP1 is a potent stress-response protein promoting p53 activity. We previously showed that ectopic overexpression of TP53INP1 facilitates cell cycle arrest as well as cell death. Here we report a study investigating cell death in mice deficient for TP53INP1. Surprisingly, we found enhanced stress-induced apoptosis in TP53INP1-deficient cells. This observation is underpinned in different cell types in vivo (thymocytes) and in vitro (thymocytes and MEFs), following different types of injury inducing either p53-dependent or-independent cell death. Nevertheless, absence of TP53INP1 is unable to overcome impaired cell death of p53-deficient thymocytes. Stress-induced ROS production is enhanced in the absence of TP53INP1, and antioxidant NAC complementation abolishes increased sensitivity to apoptosis of TP53INP1-deficient cells. Furthermore, antioxidant defenses are defective in TP53INP1-deficient mice in correlation with ROS dysregu-lation. Finally, we show that autophagy is reduced in TP53INP1-deficient cells both at the basal level and upon stress. Altogether, these data show that impaired ROS regulation in TP53INP1-deficient cells is responsible for their sensitivity to induced apoptosis. In addition, they suggest that this sensitivity could rely on a defect of autophagy. Therefore, these data emphasize the role of TP53INP1 in protection against cell injury. Antioxid. Redox Signal. 15, 1639–1653.
Embargoed file
Embargoed file
Ne sera jamais visible
Loading...

Dates and versions

inserm-01270303 , version 1 (06-02-2016)

Identifiers

Cite

Prudence N 'Guessan, Laurent Pouyet, Gaëlle Gosset, Sonia Hamlaoui, Marion Seillier, et al.. Absence of Tumor Suppressor Tumor Protein 53-Induced Nuclear Protein 1 (TP53INP1) Sensitizes Mouse Thymocytes and Embryonic Fibroblasts to Redox-Driven Apoptosis. Antioxidants and Redox Signaling, 2011, 15, pp.1639-1653. ⟨10.1089/ars.2010.3553⟩. ⟨inserm-01270303⟩
92 View
5 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More