Role of HR23B, HDAC6 and Myd88 and their interplay in response to HDAC inhibitor treatment

Abnormal epigenetic control is a common early event in tumour progression, and aberrant acetylation in particular has been implicated in tumourigenesis. Histone deacetylases (HDACs) are enzymes that regulate acetylation of chromatin and a variety of other non-histone substrates. Significantly, HDAC inhibitors are potent anti-proliferative agents and exhibit clinical activity in lymphoproliferative and haematological maligancy. However, the mechanistic details by which HDAC inhibitors affect proliferation remain to be elucidated. I have explored the cellular processes affected by HDAC inhibitors, and begun to illuminate a new pathway, regulated by HDAC, which impinges on the cellular effect of HDAC inhibitors. My results suggest that the proteins HR23B and Myd88 are important sensitivity determinants for HDAC inhibitor treatment, and that their interplay with HDAC6 dictates cell fate choice between survival by autophagy or apoptosis.This thesis is not currently available in OR