Recognition of substrate and Skp1 by the Homologue of Slimb (HOS) ubiquitin ligase receptor D role of the F-box.

Background: SCFHOS-Roc1 E3 ubiquitin ligase is an enzymatic complex, which mediates ubiquitination and subsequent proteasome-dependent degradation of phosphorylated inhibitor of NF-kB (IkB) and b-catenin. HOS is a WD40 repeats/F-box-containing protein that actually associates with the substrates and binds to Skp1 via the F-box.

Material/methods: Here, we have studied the structural determinants of the substrate recognition and ligase recruitment by HOS.

Mouse homologue of HOS (mHOS) is overexpressed in skin tumors and implicated in constitutive activation of NF-kappaB.

NF-kappaB transcription factor is activated upon ubiquitination and subsequent proteolysis of its inhibitor IkappaB. The phosphorylation-dependent ubiquitination is mediated by SCF E3 ubiquitin ligase. In this study, we identified a novel murine F-box/WD40 repeat-containing protein, mHOS (a homologue of HOS/betaTrCP2).