The development of cancer is a multi-step process involving DNA alterations, oncogene activation, and/or the inactivation/deletion of an anti-onocogene or tumor suppressor. Tumor suppressors are involved in many facets of cell biology, such as cell cycle regulation and development.
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. Abnormal nuclear localization of Cul-2 occurs in VHL (von Hippel-Lindau) syndrome, in which patients develop various cancers. Nm23 is a potential metastasis suppressor protein whose expression is either reduced, altered, or amplified in various types of metastatic carcinomas. Some of the its cellular effects are mediated by its transcriptional regulatory function, while others are mediated by its NDPK activity. The p53 protein is critical to regulation of normal cell growth and inactivation of p53 function results in tumor progression. The retinoblastoma gene product, Rb, is a nuclear phosphoprotein which undergoes differential phosphorylation during the cell cycle. It is well known as a tumor suppressor that is either absent or mutated in many human tumors. The Mutated in Colorectal Cancer (MCC) protein was identified as a tumor suppressor that is deleted in sporadic and familial colorectal cancers. Its gene is located at chromosome region 5q21, which is often associated with adenomas and carcinomas. SSeCKS (Src Suppressed C Kinase Substrate) is a tumor suppressor substrate for PKC. Its tumor suppressor function may be mediated through the actin cytoskeleton rearrangement. Thus, a variety of tumor suppressor proteins exist, which function to regulate cell growth and proliferation.