Reduced expression of the 56-kDa human selenium binding protein-1 (hSP56) has been reported in many types of human malignancies, including prostate, lung, ovarian, thyroid and colorectal cancers. hSP56 also has been implicated in selenium-dependent cell growth inhibition. However, the molecular basis of hSP56's function has not been elucidated. In the present Study, we identified von Hippel-Lindau protein (pVHL)-interacting deubiquitinating enzyme 1 (VDU1) as a protein partner of hSP56 using a yeast two hybrid screen. The interaction between hSP56 and VDU1 was confirmed by yeast two-hybrid screen and in vitro binding experiments. hSP56 and VDU1 co-localized in the perinuclear region of LNCaP human prostate cancer cells. The full-length VDU1 specifically interacted with a selenium-replete form of hsp56 We also demonstrate stable incorporation of selenium into hSP56, in a mode distinct from conventional selenocysteine-containing selenoproteins. These findings Suggest that hSP56 may play a role in ubiqui nation/deubiquitination-mediated protein degradation pathways in a selenium-dependent manner. (C) 2009 Elsevier Inc. All rights reserved.