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To Degrade or Not to Degrade, That is the Question
Author(s) -
Brooks Jeanne Kaye,
Greer Susanna F.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.lb200
Subject(s) - ciita , ubiquitin , ubiquitin ligase , microbiology and biotechnology , proteasome , deubiquitinating enzyme , biology , transcription factor , transactivation , major histocompatibility complex , chromatin remodeling , transcriptional regulation , transcription (linguistics) , protein degradation , biochemistry , immune system , mhc class ii , genetics , gene , linguistics , philosophy
The ubiquitin‐proteasome pathway plays vital roles in multiple processes including protein turnover and transcription regulation. Control of each of these pathways relies on the formation of ubiquitin‐tagged proteins via a series of enzymatic reactions resulting in the addition of ubiquitin molecules to lysine residues within target proteins. The fate of the ubiquitinated protein is determined by both the number of ubiquitin molecules and the site to which they are added. Proteins that are mono‐ubiquitinated have been shown to be involved in chromatin remodeling, DNA repair, and transcriptional activation, while polyubiquitinated proteins are targeted to the 26S proteasome for degradation. Major histocompatibility complex class II (MHC‐II) molecules are a vital part of the adaptive immune response and are responsible for presenting exogenous antigens to CD4+ T cells. The class II transactivator (CIITA) is the master regulator of MHC‐II transcription and has been shown to have increased transactivity in the presence of monoubiquitin. Our study highlights the impact of CIITA ubiquitination on the expression of MHC‐II genes by identifying the E3 ligase responsible for CIITA ubiquitination. This research will improve our understanding of the regulation of activation and half‐life of CIITA and of the transcriptional regulation of MHC‐II expression. Research supported by The American Cancer Society.