An Unbiased Approach To Identify Endogenous Substrates of “Histone” Deacetylase 8

Despite being extensively characterized
structurally and biochemically,
the functional role of histone deacetylase 8 (HDAC8) has remained
largely obscure due in part to a lack of known cellular substrates.
Herein, we describe an unbiased approach using chemical tools in conjunction
with sophisticated proteomics methods to identify novel non-histone
nuclear substrates of HDAC8, including the tumor suppressor ARID1A.
These newly discovered substrates of HDAC8 are involved in diverse
biological processes including mitosis, transcription, chromatin remodeling,
and RNA splicing and may help guide therapeutic strategies that target
the function of HDAC8.