Premium
Association of the 19S proteasomal ATPases with the ATPase‐binding domain of CIITA is essential for CIITA stability and MHC class II expression
Author(s) -
Bhat Kavita Purnanda,
Truax Agnieszka Dorota,
Brooks Jeanne Kaye,
Greer Susanna Fletcher
Publication year - 2010
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2010.45
Subject(s) - ciita , biology , microbiology and biotechnology , mhc class i , proteasome , mhc class ii , cd74 , antigen processing , major histocompatibility complex , genetics , immune system
Major histocompatibility class II (MHC class II) molecules are glycoproteins that present extracellular antigens to CD4 + T cells and are essential for initiation of adaptive immune responses. MHC class II expression requires recruitment of a master regulator, the class II transactivator (CIITA), to the MHC class II promoter. Others and we have earlier linked CIITA to the ubiquitin‐proteasome system by showing that mono‐ubiquitination of CIITA increases its transactivity, whereas poly‐ubiquitination of CIITA leads to its degradation. We have further shown that the 26S proteasome also has non‐proteolytic functions in MHC class II transcription, as 19S ATPase subunits of the 26S proteasome positively regulate MHC class II transcription and are necessary for stable promoter binding of CIITA. Although these basic requirements of the proteasome to initiate MHC class II transcription are known, how CIITA is recruited, stabilized, and degraded remains unclear. Here, we identify a novel N‐terminal 19S ATPase‐binding domain of CIITA. The ATPase‐binding domain lies within the proline/serine/threonine‐rich region of CIITA and encompasses a majority of the CIITA degron sequence. Absence of the ATPase‐binding domain increases the half‐life of CIITA, but blocks MHC class II surface expression, indicating that CIITA requires interaction with the 19S ATPases for both appropriate deployment and destruction.