The cullins are a family of proteins that are integral to cell cycle regulation. Members of this family include human Cul-2, 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. Abnormal nuclear localization of Cul-2 is seen in a rare hereditary condition known as VHL (von Hippel-Lindau) syndrome. Patients with VHL syndrome possess a mutant VHL gene and develop cancers such as retinal anginomas, CNS hemangioblastomas, and renal cell carcinomas. In normal cells, the VHL protein competes with subunit A of elongin, a transcription elongation factor, for binding to subunits B and C. The formation of the VHL-B-C complex inhibits elongation. Additional data indicates that this complex associates with CUL-2 and promotes CUL-2 nuclear translocation. In cells with mutated VHL, transcriptional elongation is not efficiently curtailed and CUL-2 is not properly localized in the nucleus. Therefore, CUL-2 mediates VHL function, suggesting CUL-2 may be a candidate human tumor suppressor.
This antibody is routinely tested by western blot analysis. Other applications were tested at BD Biosciences Pharmingen during antibody development only or reported in the literature.