Histone deacetylase 7 (HDAC7) promotes PML sumoylation

The promyelocytic leukemia (PML) protein is a nuclear phosphoprotein, originally isolated as a fusion partner of human retinoic acid receptor alpha involved in acute promyelocytic leukemia (APL). PML is enriched in nuclear discrete structures, alternatively called Kremer (Kr) bodies, nuclear domain 10 (ND10), PML oncogenic domains (PODs), or PML nuclear bodies (NBs). PML is an essential component of PML NBs and loss of PML results in loss of PML NBs. Sumoylation of PML is essential for the formation of PML NBs, but the mechanisms controlling PML sumoylation and homeostasis are largely unknown. Histone deacetylase 7 (HDAC7) is a member of class II HDAC family that plays a pivotal role in cellular processes and organ development, including muscle differentiation, heart development, thymus development, and skeletogenesis. Recently, it was reported that class II HDACs such as HDAC4 stimulates sumoylation of MEF2 transcription factors. Using confocal microscopy, we show that HDAC7 is partially colocalized with PML NBs. We demonstrate that HDAC7 interacts with PML in mammalian cells and potentiates PML sumoylation. The ability to stimulate PML sumoylation does not require C‐terminal HDAC catalytic domain. We have also isolate dominant‐negative HDAC7 mutants that, when overexpressed, inhibit PML sumoylation. Taken together, our data suggest that HDAC7 is an E3 ligase for PML sumoylation and that class II HDACs are E3 ligases for a subset of sumoylated cellular proteins. This study is supported by National Institute of Health and American Cancer Society.