Back to Search
Start Over
N-terminal destruction signals lead to rapid degradation of the major histocompatibility complex class II transactivator CIITA.
- Source :
-
European journal of immunology [Eur J Immunol] 2003 Aug; Vol. 33 (8), pp. 2337-47. - Publication Year :
- 2003
-
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.
- Subjects :
- Amino Acid Sequence
Cell Line
Cysteine Endopeptidases metabolism
Drug Stability
Half-Life
Humans
Molecular Sequence Data
Multienzyme Complexes metabolism
Proteasome Endopeptidase Complex
Protein Sorting Signals genetics
Protein Structure, Tertiary
Sequence Deletion
Trans-Activators genetics
Transfection
Ubiquitin metabolism
Genes, MHC Class II
Nuclear Proteins
Trans-Activators chemistry
Trans-Activators metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0014-2980
- Volume :
- 33
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- European journal of immunology
- Publication Type :
- Academic Journal
- Accession number :
- 12884309
- Full Text :
- https://doi.org/10.1002/eji.200323490