N-terminal destruction signals lead to rapid degradation of the major histocompatibility complex class II transactivator CIITA Journal Article
| Authors: | Schnappauf, F.; Hake, S. B.; Camacho-Carvajal, M. M.; Bontron, S.; Lisowska-Grospierre, B.; Steimle, V. |
| Article Title: | N-terminal destruction signals lead to rapid degradation of the major histocompatibility complex class II transactivator CIITA |
| Abstract: | Major histocompatibility complex (MHC) class II molecules play an essential role for the cellular immune response by presenting peptide antigens to CD4+ T cells. MHC class II molecules and genes show a highly complex expression pattern, which is orchestrated through a master regulatory factor, called CIITA (class II transactivator). CIITA controls MHC class II expression not only qualitatively, but also quantitatively, and has therefore a direct influence on the CD4 T cell-dependent immune response. CIITA is itself tightly regulated not only on the transcriptional level, but as we show here also on the protein level. CIITA is subjected to a very rapid protein turnover and shows a half-life of about 30 min. Inhibition of degradation by proteasome inhibitors and the identification of ubiquitylated CIITA intermediates indicate that the degradation of CIITA is mediated by the ubiquitin-proteasome system. We identified two regions mediating degradation within the N-terminal domain of CIITA. N-terminal fusions or deletions stabilized CIITA, indicating that the N termini contribute to degradation. Several non-functional CIITA mutants are partially stabilized, but we provide evidence that transcriptional activity of CIITA is not directly linked to degradation. |
| Keywords: | controlled study; human cell; promoter region; sequence deletion; ubiquitin; protein function; t lymphocyte; proteasome inhibitor; proteasome endopeptidase complex; gene expression; protein degradation; protein metabolism; cell line; transfection; nuclear proteins; cellular immunity; immune response; amino acid sequence; molecular sequence data; amino terminal sequence; quantitative analysis; transactivator protein; major histocompatibility antigen class 2; protein structure, tertiary; trans-activators; cd4 antigen; major histocompatibility complex; genes, mhc class ii; multienzyme complexes; half life time; antigen presenting cell; drug stability; half-life; mutant; regulator protein; qualitative analysis; molecular stability; ubiquitin-proteasome system; cysteine endopeptidases; protein sorting signals; humans; human; priority journal; article; mhc class ii gene regulation |
| Journal Title: | European Journal of Immunology |
| Volume: | 33 |
| Issue: | 8 |
| ISSN: | 0014-2980 |
| Publisher: | Wiley V C H Verlag Gmbh |
| Date Published: | 2003-08-01 |
| Start Page: | 2337 |
| End Page: | 2347 |
| Language: | English |
| DOI: | 10.1002/eji.200323490 |
| PUBMED: | 12884309 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
