The cullins are a family of proteins that are integral to cell cycle regulation. Members of this family include human Cul proteins, C.elegans Ce-Cul-1, and S. cerevisiae Cdc53. Proper control of cell cycle progression is essential for the prevention of tumorigenesis. Mutant forms of both Ce-Cul-1 and Cdc53 have been implicated in the oncogenic process. The human Cul family of proteins, Cul-1, -2, -3, -4A, -4B, and -5, have also been implicated in oncogenic processes. Abnormal nuclear localization of Cul-2 is seen in the VHL (von Hippel-Lindau) syndrome, which includes development of a variety of cancers. Cul-3 is widely expressed in normal cells, and has increased expression in colon cancer cells. Cul-3 can associate with cyclin E in mammalian cells, and overexpression of Cul-3 targets cyclin E for ubiquination. Cul-1 associates with the ubiquination-conjugating complex, cyclin A/CDC34/p45[SKP2]/p19[SKP1]. In addition, Cul-1 interacts with p19[SKP1], E2 ubiquination-conjugating enzyme, and FWD1 to facilitate ubiquitin degradation of IkappaBalpha, beta.catenin, and Vpu proteins. Thus, Cul-1, as well as other cullin family members, may have important roles in cycle-dependent ubiquitin degradation.