HDAC6 regulates the protein stability and tumor suppressor function of HIPK2 independently of its deacetylase...

HIPK2 is a tumor suppressor and a key regulator of cellular stress responses. In the present study we present evidence that HDAC6 regulates HIPK2 protein stability via its ubiquitin-binding domain. HDAC6 increased the protein stability of HIPK2 independently of its deacetylase activity. Interestingly, ubiquitin-binding domain of HDAC6 was sufficient for this regulation on HIPK2. HDAC6 decreased the polyubiquitination of HIPK2, suggesting that HDAC6 may promote deubiquitination or inhibit ubiquitination of HIPK2. We also found evidence that HDAC6 and HIPK2 form complex in cells. Importantly, HDAC6 enhanced the tumor suppressor function of HIPK2. Taken together, our present data identify a novel HIPK2 regulation mechanism mediated by HDAC6.