Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0079731 (B-cell lymphoma)
 16,671 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ubiquitination of proteins by E3 ligases has become an important regulatory mechanism for a variety of immune functions, including the maintenance of self tolerance and suppression of autoreactive T cell development. This review highlights recent advances in our knowledge of the functions in this context of known and potential E3 ligases, including autoimmune regulator (AIRE), TNF receptor-associated factor 6 (TRAF6), Casitas B cell lymphoma b (Cbl-b), gene related to anergy in lymphocytes (GRAIL), Itch, and Roquin. We discuss how disruptions to these molecules may contribute to the loss of T cell homeostasis and the pathogenesis of autoimmunity. We also report on the implications of the potential coordinated actions of these molecules for T cell anergy and regulatory T cell (Treg) functions. The great diversity of E3 ligases and the growing list of cellular processes in which ubiquitination plays a role make for an exciting field of research. Findings emerging from these investigations may suggest ways to exploit the therapeutic potential of manipulating ubiquitination, particularly for autoimmune disorders.
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PMID:The role of E3 ligases in autoimmunity and the regulation of autoreactive T cells. 1803 6

The activation of T cells is tightly controlled by many positive and negative regulatory processes. This fine-tuning allows productive immunity to pathogens while minimizing the risk of autoimmunity. One negative regulatory mechanism is clonal anergy, which is a hyporesponsive state that occurs when T cells are activated through the T-cell antigen receptor in the absence of appropriate co-stimulatory signals. Recent studies have confirmed a crucial role for defective Ras activation in mediating this hyporesponsive state. Diminished Ras activation can, in part, be explained by the upregulated expression of diacylglycerol kinases (DGKs), which phosphorylate diacylglycerol and restrict Ras guanyl releasing protein 1 (RasGRP1)-dependent activation of Ras. Increased expression of DGKs is probably transcriptional and is accompanied by augmented expression of additional negative regulators, including the transcription factors early growth response (Egr) 2 and Egr3, and the E3 ubiquitin ligases known as gene related to anergy in lymphocytes (GRAIL) and Casitas B-cell lymphoma-b (Cbl-b). A model is emerging for how these factors are regulated to control T-cell responsiveness.
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PMID:Molecular regulation of T-cell anergy. 1817 97