e3 ubiquitin ligases and their control of t cell autoreactivitye3泛素连接酶的t细胞autoreactivity及其控制.pdfVIP

Available online /content/7/6/233 Review E3 ubiquitin ligases and their control of T cell autoreactivity Jody L Bonnevier, Ruan Zhang and Daniel L Mueller Rheumatic and Autoimmune Diseases Division, and Center for Immunology, University of Minnesota Medical School, Minneapolis, MN, USA Corresponding author: Daniel L Mueller, muell002@ Published: 12 October 2005 Arthritis Research Therapy 2005, 7:233-242 (DOI 10.1186/ar1842) This article is online at /content/7/6/233 © 2005 BioMed Central Ltd Abstract the cell cycle, modulation of cell surface receptors, cellular A loss of T cell tolerance underlies the development of most differentiation, DNA repair, gene transcription, and cellular autoimmune diseases. The design of therapeutic strategies to re- stress responses. In the innate immune system, ubiquitin- institute immune tolerance, however, is hampered by uncertainty dependent proteasomal degradation of foreign proteins regarding the molecular mechanisms involved in the inactivation of mediates antigen presentation. Furthermore, the activation of potentially autoreactive T cells. Recently, E3 ubiquitin ligases have the proinflammatory cytokine gene transactivator nuclear been shown to mediate the development of a durable state of factor κB (NFκB) relies on ubiquitin-mediated degradation of unresponsiveness in T cells called clonal anergy. In this review, we will discuss the mechanisms used by E3 ligases to control the the IκBα inhibitory protein at sites of infection and/or activation of T cell