SUMO4 and its role in type 1 diabetes pathogenesis.
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.
Wang
Cong-Yi
CY
Center for Biotechnology and Genomic Medicine, Department of Pathology, Medical College of Georgia, Augusta, GA 30912, USA. cwang@mcg.edu
She
Jin-Xiong
JX
D044466:Asian People / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology* / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D053612:Janus Kinases / Q000037:antagonists & inhibitors; D016328:NF-kappa B / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D050791:STAT Transcription Factors / Q000037:antagonists & inhibitors; D015398:Signal Transduction; D025841:Small Ubiquitin-Related Modifier Proteins / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D044465:White People / Q000235:genetics
D016328:NF-kappa B; D050791:STAT Transcription Factors; C489647:SUMO4 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; D018808:Transcription Factor AP-1; D053612:Janus Kinases