Nedd4 family interacting protein 1 (Ndfip1) promotes death of pancreatic beta cells - PubMed (original) (raw)

. 2015 Oct 2;465(4):851-6.

doi: 10.1016/j.bbrc.2015.08.099. Epub 2015 Aug 28.

Affiliations

Nedd4 family interacting protein 1 (Ndfip1) promotes death of pancreatic beta cells

Avital Beck et al. Biochem Biophys Res Commun. 2015.

Abstract

High-throughput siRNA screening was employed to identify novel genes that regulate cytokine-induced death of pancreatic β-cells. One of the 'hits' was Nedd4 family interacting protein 1 (Ndfip1), an adaptor and activator of Nedd4-family ubiquitin ligases. Silencing of Ndfip1 inhibited cytokine-induced apoptosis of mouse and human pancreatic islets and promoted glucose-stimulated insulin secretion. These effects were associated with an increase in the cellular content of JunB, a potent inhibitor of ER stress and apoptosis. Silencing of Ndfip1 also increased the expression of ATF4, IRE-1α, and the spliced form of XBP that govern the unfolded protein response (UPR) and relieve cytokine-induced ER stress, while overexpression of Ndfip1 exerted opposite effects. These findings implicate Ndfip1 in the degradation of JunB; inhibition of the UPR and insulin secretion; and promotion of cytokine-induced death of pancreatic β-cells.

Keywords: Cytokines; JunB; Ndfip1; Pancreatic beta cells; Unfolded protein response.

Copyright © 2015 Elsevier Inc. All rights reserved.

PubMed Disclaimer

Publication types

MeSH terms

Substances

LinkOut - more resources