Regulating the activity of class II transactivator by posttranslational modifications: exploring the possibilities

Abstract

First identified as the master regulator of major histocompatibility complex II transcription, class II transactivator (CIITA) has since been implicated in a host of pathologies by modulating the transcription of multiple different genes. How CIITA caters to cell- and tissue-specific transcriptional needs is hotly debated and investigated. One of the possible mechanisms underlying spatiotemporal control of CIITA transcriptional activity is the posttranslational modification (PTM) machinery that refines certain amino acid residues of CIITA and hence alters its activity in response to specific cellular and environmental cues. This review discusses our current understanding of the PTM map of CIITA, how these modifications fine-tune its activity, and how the study of this area may lead to potential therapeutic strategies.

FIG. 1.

A schematic map of known modification sites in CIITA. AD, activation domain; AT, acetyltransferase domain; PST, PST domain; GBD, GTP binding domain.

FIG. 2.

PTMs manipulate CIITA activity by different mechanisms. Specific covalent modifications can alter the subcellular localization of CIITA (A), interactions of CIITA with other factors and promoter selectivity (B and C), or stability of the CIITA protein (D).