Endoplasmic reticulum stress induces the degradation of SCD protein via ubiquitin-proteasome pathway

Tuesday, October 09, 2012 — Poster Session I
1:00 p.m. – 3:00 p.m	Natcher Conference Center, Building 45	NEI	APO-2

* FARE Award Winner

Authors

• W. Samuel
• R.K. Kutty
• T. Duncan
• T.M. Redmond

Abstract

Perturbations to endoplasmic reticulum (ER), the central organelle for protein biosynthesis and maturation, can cause ER stress, and if unchecked could lead to apoptosis. Stearoyl-CoA desaturase (SCD), an ER resident protein and a key enzyme in the biosynthesis of monounsaturated fatty acids, is known to regulate cellular functions by controlling the ratio of saturated to monounsaturated fatty acids. SCD has been reported to be degraded through both ubiquitin-proteasome-dependent and-independent pathways when overexpressed in cells. The purpose of this study was to determine whether ER stress affects the expression of SCD protein. Human retinal pigment epithelial (ARPE-19) cells treated with N-(4-hydroxyphenyl)retinamide (4HPR), tunicamycin and thapsigargin, compounds known to induce ER stress, showed a time-dependent decrease in the expression of SCD protein, while, BiP/GRP78, a protein marker for ER stress, was markedly increased. The decrease in SCD protein expression was completely blocked by the proteasome inhibitor, MG132. Immunoprecipitation analysis of 4HPR-treated cell lysate using ubiquitin antibody showed that ER stress increased the ubiquitination of proteins including SCD. Thus, these data show that ER stress mediates the degradation of SCD in human RPE cells via the ubiquitin-proteasome dependent pathway

back to top