The interaction between endogenous VHL and HDAC6 in retinal tissues from control and OIR mice was examined by immunoprecipitation and immunoblotting.
Our data also demonstrate that the continuous increase in the HDAC6 level results from the persistent activation of ASK1 in response to oxygen changes; ASK1-mediated phosphorylation of HDAC6 blocks its degradation via the ubiquitin-proteasome pathway.
The regulation of HDAC6 by VHL is reminiscent of its action in the control of hypoxia inducible factor-1α (HIF-1α). Under normoxic conditions, oxygen-dependent prolyl hydroxylation of HIF-1α promotes its interaction with VHL, leading to the ubiquitination and proteasomal degradation of HIF-1α; by contrast, under hypoxia, the above ubiquitin-dependent proteolysis of HIF-1α does not occur, resulting in its stabilization (Ivan et al., 2001, Jaakkola et al., 2001).