MAD2L1 (D8A7) Rabbit mAb #4636

Correct segregation of sister chromatids prior to the onset of cell division is essential to the maintenance of genetic integrity and the avoidance of aneuploidy and chromosomal instability, characteristics of many cancer cells. The mitotic checkpoint, also known as the spindle assembly checkpoint, monitors accurate attachment of kinetochores to the spindle, inhibits mitosis and delays the onset of anaphase until all chromosomes are aligned at the metaphase plate (1). MAD2L1 is an essential participant in the mitotic checkpoint (2). It exists in two conformations, including the open and inactive O-MAD2 form and the closed, active C-MAD2 form. Prior to mitosis, MAD2L1 is localized to the cytosol and exists largely in the closed, inactive form. During the mitotic checkpoint, MAD2L1 switches to the open, active conformation (3). Together with other checkpoint proteins, MAD2L1 binds to and deactivates Cdc20, thereby inhibiting the anaphase promoting complex (4). When the kinetochores are correctly attached to the spindle, MAD2L1 releases Cdc20, which allows activation of the anaphase promoting complex and subsequent degradation of key mitotic substrates and the initiation of metaphase-anaphase transition (5).