The interaction of the von Hippel-Lindau tumor suppressor and heterochromatin protein 1

► Our proteomic screening detected the interaction of VHL and HP1. ► We identified a conserved HP1-binding motif (PXVXL) in VHL. ► This HP1-binding motif is disrupted in renal carcinoma-associated VHL P81S mutant. ► VHL P81S mutant displays reduced HP1 interaction, but is able to degrade HIF-α. ► HP1 increased the chromatin association of VHL30.