Journal article

N-terminal destruction signals lead to rapid degradation of the major histocompatibility complex class II transactivator CIITA


Authors listSchnappauf, F; Hake, SB; Carvajal, MMC; Bontron, S; Lisowska-Grospierre, B; Steimle, V

Publication year2003

Pages2337-2347

JournalEuropean Journal of Immunology

Volume number33

Issue number8

ISSN0014-2980

DOI Linkhttps://doi.org/10.1002/eji.200323490

PublisherWiley


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.



Citation Styles

Harvard Citation styleSchnappauf, F., Hake, S., Carvajal, M., Bontron, S., Lisowska-Grospierre, B. and Steimle, V. (2003) N-terminal destruction signals lead to rapid degradation of the major histocompatibility complex class II transactivator CIITA, European Journal of Immunology, 33(8), pp. 2337-2347. https://doi.org/10.1002/eji.200323490

APA Citation styleSchnappauf, F., Hake, S., Carvajal, M., Bontron, S., Lisowska-Grospierre, B., & Steimle, V. (2003). N-terminal destruction signals lead to rapid degradation of the major histocompatibility complex class II transactivator CIITA. European Journal of Immunology. 33(8), 2337-2347. https://doi.org/10.1002/eji.200323490


Last updated on 2025-21-05 at 15:34