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Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1) is a key component of the spindle assembly checkpoint (SAC), a surveillance mechanism that prevents the onset of anaphase until all chromosomes are properly attached and aligned at the metaphase plate during mitosis[2][3]. MAD2L1 plays a critical role by binding to CDC20, thereby inhibiting the activation of the anaphase-promoting complex/cyclosome (APC/C) and delaying cell cycle progression until correct chromosome alignment is achieved[3][5]. Loss of MAD2L1 function compromises chromosome segregation fidelity and can lead to aneuploidy, a hallmark of many cancers and specific syndromes such as mosaic variegated aneuploidy[2][6]. The protein interacts with several key mitotic regulators, including BUB1B, CDC20, and others[3]. Therapeutically, MAD2L1 is targeted by small molecule inhibitors like M2I-1, which disrupt MAD2-CDC20 interactions and SAC function[4]. Loss or dysregulation of MAD2L1 is associated with an increased risk of tumorigenesis and may serve as a biomarker for chromosomal instability in cancers[6].
Inhibition of MAD2-CDC20 protein-protein interaction; Disruption of spindle assembly checkpoint
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