Major histocompatibility (MHC) class II molecules are cell surface glycoproteins 
that present extracellular antigens to CD4(+) T cells and are essential for 
initiation of the adaptive immune response. MHC class II expression requires 
recruitment of a master regulator, the class II transactivator (CIITA), to the 
MHC class II promoter. Post-translational modifications to CIITA play important 
roles in modulating CIITA mediated transcription of various genes in different 
cell types. We have previously linked regulation of CIITA to the Ubiquitin 
Proteasome System (UPS), and we and others have demonstrated that 
mono-ubiquitination of CIITA dramatically increases its transactivity whereas 
poly-ubiquitination leads to CIITA degradation. Here we identify three degron 
proximal lysine residues, Lys-315, Lys-330, and Lys-333, and a phosphorylation 
site, Ser-280, located within the CIITA degron, that regulate CIITA 
ubiquitination, stability, and MHC class II expression. Together, these findings 
contribute to the developing post-translational modification code for CIITA.