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

Biochemical and Biophysical Research Communications
Avital BeckYehiel Zick

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.

References

Dec 19, 2001·The Journal of Biological Chemistry·Kieran F HarveySharad Kumar
Oct 31, 2003·Biochimie·M AmeyarJ B Weitzman
Jun 15, 2007·Nature Reviews. Molecular Cell Biology·David Ron, Peter Walter
Dec 1, 2007·Endocrine Reviews·Marc Y DonathThomas Mandrup-Poulsen
Aug 22, 2008·PloS One·Esteban N GurzovDecio L Eizirik
Sep 30, 2008·The Journal of Biological Chemistry·Ulrich PutzSeong-Seng Tan
Apr 4, 2009·EMBO Reports·Thomas Mund, Hugh R B Pelham
May 14, 2009·Nature Reviews. Molecular Cell Biology·Daniela Rotin, Sharad Kumar
Sep 7, 2012·Cold Spring Harbor Perspectives in Medicine·Feroz R Papa
Feb 13, 2014·Proceedings of the National Academy of Sciences of the United States of America·John A AltinChristopher C Goodnow
May 3, 2014·Cell Death and Differentiation·D A CunhaM Cnop

❮ Previous
Next ❯

Citations

Dec 10, 2016·Physiological Reviews·Natalie FootSharad Kumar

❮ Previous
Next ❯

Related Concepts

Related Feeds

B-Cell Lymphoma

B-cell lymphomas include lymphomas that affect B cells. This subtype of cancer accounts for over 80% of non-Hodgkin lymphomas in the US. Here is the latest research.

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis