Target intelligence / Profile preview

Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1)

Target
MAD2L1
Molecular classification
Cell cycle regulator, Spindle assembly checkpoint protein, Checkpoint control protein, Other
01

Overview

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].

Other names
Mitotic arrest deficient 2 like 1MAD2HsMAD2MAD2-like protein 1HSMAD2Mitotic arrest deficient 2-like protein 1mitotic arrest deficient, yeast, homolog-like 1MAD2 mitotic arrest deficient-like 1MAD2A
02

Mechanism of action

Inhibition of MAD2-CDC20 protein-protein interaction; Disruption of spindle assembly checkpoint

03

Biological functions

Cell cycle controlMitosis regulationSpindle assembly checkpoint (SAC)Chromosome segregation fidelity
04

Disease associations

CancerAneuploidy syndromes (e.g. Mosaic Variegated Aneuploidy Syndrome)Other
05

Safety considerations

Disruption can cause chromosomal instability and promote tumorigenesisLoss of MAD2L1 function may allow cancer cell proliferation and tumor acceleration, especially in p53-deficient backgrounds
06

Interacting drugs

Mad2 Inhibitor-1 (M2I-1)
07

Biomarkers

Aneuploidy markers (for syndromes)Potential cancer prognosis marker

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