Is a New Immune Response Mediator in the NF-κB pathway - SUMO-4 - Related to Type 1 Diabetes?

Abstract

The Review of Diabetic Studies,2005,2,2,58-60.DOI:10.1900/RDS.2005.2.58Published:May 2005Type:EditorialAuthors:Charles Sia Author(s) affiliations:Charles Sia Department of Immunology, United Biomedical Inc., 25 Davids Drive, Hauppage, New York 11788, USA. Abstract:Type 1 diabetes mellitus (T1DM) is hallmarked by a complete loss of insulin secretion capacity caused by T cell-mediated destruction of pancreatic β-cells [1, 2]. The disorder has a complex pathogenesis involving genetic and environmental factors, it appears impossible hitherto to explain sufficiently how islet abnormalities arise and which mechanisms trigger immune cells to become diabetogenic. However, we already know that a series of immune-responsive mediators are involved in the occurrence of autoimmunity and the damage of β-cells; the most critical mediators are MHC class I and II molecules, cytotoxic enzymes and cytokines, such as interleukin-1β (IL-1β) and interferon-γ (IFN-γ) [3]. IL-1β and IFN-γ, which are potential mediators of islet inflammation and contributors of β-cell death [4], modify the expression of a number of genes in β-cells by themselves. But indirectly these mechanisms are regulated by transcriptional modifiers through pathways involving the nuclear transcription factor NF-κB [5], the activation of which is regarded as pro-apoptotic in pancreatic β-cells [6, 7]. Elevated activation of NF-κB has been shown to implicate the destruction of β-cells and the development of T1DM [8]. NF-κB was further demonstrated to be associated with T1DM [9, 10] and deficiency in this transcriptional regulator even prevents mice from streptozotocininduced diabetes [11, 12]. One of the modifiers of NF- κB is a newly discovered post-transcriptional protein modifier which is, due to its functional and structural similarity with ubiquitin, called the small ubiquitin-like modifier (SUMO). Read more... Keywords:NilView:PDF (276.68 KB)