SUMO4 and its role in type 1 diabetes pathogenesis

• Published in: Diabetes/metabolism research and reviews 2008-02, Vol.24 (2), p.93-102
• Main Authors: Wang, Cong-Yi, She, Jin-Xiong
• Format: Article
• Language: English
• Subjects: AP-1; apoptosis; Asian Continental Ancestry Group - genetics; association; autoimmunity; cytokines; Diabetes Mellitus, Type 1 - etiology; Diabetes Mellitus, Type 1 - genetics; European Continental Ancestry Group - genetics; genetic heterogeneity; Genetic Predisposition to Disease; Humans; IκBα; JAK/STAT; Janus Kinases - antagonists & inhibitors; linkage; NF-kappa B - physiology; NFκB; oxidative stress; Oxidative Stress - drug effects; Oxidative Stress - physiology; pathogenesis; PIAS; Signal Transduction; Small Ubiquitin-Related Modifier Proteins - physiology; STAT Transcription Factors - antagonists & inhibitors; SUMO; sumoylation; susceptibility; Transcription Factor AP-1 - antagonists & inhibitors; Transcription Factor AP-1 - metabolism
• ISSN: 1520-7552; 1520-7560
• DOI: 10.1002/dmrr.797

Susceptibility to type 1 diabetes (T1D) is determined by interactions of multiple genes with unknown environmental factors. Despite the characterization of over 20 susceptibility regions for T1D, identification of specific genes in these regions is still a formidable challenge. In 2004, we first reported the cloning of a novel, small ubiquitin‐like modifier (SUMO) gene, SUMO4, in the IDDM5 interval on chromosome 6q25, and presented strong genetic and functional evidence suggesting that SUMO4 is a T1D susceptibility gene. Subsequent studies have consistently confirmed this association in multiple Asian populations despite controversial observations in Caucasians. In this review, we will update the genetic evidence supporting SUMO4 as a T1D susceptibility gene and discuss the possible explanations for the discrepant associations observed in Caucasians. We will then discuss the mechanisms through which SUMO4 contributes to the pathogenesis of T1D. Copyright © 2007 John Wiley & Sons, Ltd.