MAD2 is a mitotic checkpoint gene whose function is required for yeast cells to arrest before undergoing cell division if the mitotic spindle apparatus is improperly attached to the chromosomes. In the absence of functional MAD2 protein, yeast cells that are exposed to drugs that inhibit the formation of a mitotic spindle, such as benomyl, vinblastine, and nocodazole, undergo rapid death due to massive chromosome loss. The human homolog of MAD2 is the first identified human gene that serves as a checkpoint for cells in their progress into the final stage of cell division.
A human breast tumor cell line sensitive to the anticancer drugs Taxol and nocodazole, has low levels of MAD2. Tumor cells that are hypersensitive to chemotherapeutic agents that inhibit the formation of the mitotic spindle may be sensitive to these drugs because they are defective in the MAD2 checkpoint. Analysis of the MAD2 status of a given tumor may therefore be a predictor of chemosensitivity. The loss of MAD2 function in a normal cell may predispose that cell to aberrant chromosome segregation events, a hallmark of tumor progression. Manipulating the level of MAD2 in tumor cells can make the tumor cells susceptible to mitotic spindle inhibitors.
Diagnostic, therapeutic, and research tool
Anti-MAD2 antibody and MAD2 probes available for licensing.
Robert Benezra, PhD, Laboratory Head, Cancer Biology and Genetics Program, Sloan Kettering Institute, Memorial Sloan Kettering
U.S. patent issued: 6,096,522
Li Y, Benezra R. (1996) Science. 274(5285):246-8