Figure 8. We propose CIITA IF3 is modified by Lys⁶³-linked ubiquitination while in the cytoplasm by an unknown E3 Ub ligase.

Lys⁶³-linked ubiquitinated CIITA is phosphorylated by the kinase complex, ERK1/2 at Ser²⁸⁰, which allows for CIITA to translocate to the nucleus where CIITA acts as the master regulator for the MHC II genes. It is clear that mono-ubiquitination is necessary for CIITA transactivity; however, it is unclear if mono-ubiquitination occurs in the cytoplasm or nucleus.