Abstract
MHC II molecules are glycoproteins that present intracellular antigens to CD4+ T cells and play an important role in induction and regulation of adaptive immune responses. MHC II molecules are regulated at the level of transcription by a master regulator, the class II transcriptional activator, CIITA, whose association with the MHC promoter is necessary for initiation of transcription. It is well established that one mechanism of regulating transcription is through degradation of factors by the 26S proteasome. The proteasome is composed of a 19S regulatory particle that recognizes ubiquitinated proteins and a 20S proteolytic core where the tagged proteins are degraded. Previous studies in yeast have demonstrated that the S6a ATPase of the 19S associates with actively transcribed genes, suggesting a non-degradative role for the ubiquitin-proteasome machinery. To further understand these roles in mammalian cells, we have investigated the role of S6a in regulating CIITA mediated MHC II transcription. Our research indicates that S6a is recruited to actively transcribing MHC II and CIITA genes and that RNAi mediated S6a knockdown correlates with decreased expression of MHC II and CIITA. Our study demonstrates a novel mechanism of regulating MHC II expression and will enhance our understanding of mammalian transcription.
Research supported by the NMSS, the Georgia Cancer Coalition and GSU.