MAD2 Mitotic Arrest Deficient-Like 1 Human Recombinant
MAD2L1 Human Recombinant produced in E.Coli is a single, non-glycosylated polypeptide chain containing 225 amino acids (1-205 a.a.) and having a molecular mass of 25.7kDa.
MAD2L1 is fused to a 20 amino acid His-tag at N-terminus & purified by proprietary chromatographic techniques.
MAD2L1 Binding Protein Human Recombinant
MAD2, also known as Mitotic Arrest Deficient 2, is a crucial component of the spindle assembly checkpoint (SAC) system. This protein plays an essential role in ensuring accurate chromosome segregation during cell division by preventing the onset of anaphase until all chromosomes are properly aligned . MAD2 is classified as a spindle checkpoint protein and is part of the MAD/BUB complex .
Key Biological Properties: MAD2 is a small protein with a molecular weight of approximately 24 kDa . It exists in two conformations: open (O-MAD2) and closed (C-MAD2), with the latter being more active in inhibiting the anaphase-promoting complex/cyclosome (APC/C) .
Expression Patterns: MAD2 is expressed at high steady-state levels in various tissues. It is predominantly localized at unattached kinetochores during mitosis .
Tissue Distribution: MAD2 is found in multiple tissues, including muscle, testis, thyroid gland, cerebrum, trachea, and skin. In cancerous tissues, such as gastric cancer, MAD2 shows altered expression patterns, often being overexpressed .
Primary Biological Functions: MAD2 is a central component of the spindle assembly checkpoint, which ensures proper chromosome alignment and segregation during mitosis . It inhibits the APC/C by binding to its activator, Cdc20, thereby delaying anaphase onset until all chromosomes are correctly attached to the spindle .
Role in Immune Responses and Pathogen Recognition: While MAD2’s primary role is in cell division, its involvement in immune responses and pathogen recognition is not well-documented. However, its function in maintaining genomic stability indirectly supports immune system integrity by preventing aneuploidy and potential oncogenesis .
Mechanisms with Other Molecules and Cells: MAD2 interacts with several key proteins, including Mad1 and Cdc20. Mad1 recruits MAD2 to unattached kinetochores, where MAD2 binds to Cdc20, forming the mitotic checkpoint complex (MCC) .
Binding Partners: MAD2 binds to Mad1 and Cdc20, forming stable complexes that inhibit APC/C activity . The interaction between MAD2 and Cdc20 is regulated by the conformational switch between O-MAD2 and C-MAD2 .
Downstream Signaling Cascades: The binding of MAD2 to Cdc20 prevents the activation of APC/C, thereby inhibiting the degradation of securin and cyclin B. This delay in anaphase onset ensures proper chromosome alignment and segregation .
Transcriptional Regulation: The expression of MAD2 is regulated at the transcriptional level by various factors, including E2F1 and the retinoblastoma protein (pRb) .
Post-Translational Modifications: MAD2 undergoes several post-translational modifications, including phosphorylation. Phosphorylation at Ser195 has been shown to affect its function in the spindle checkpoint and its sensitivity to radiotherapy in cancer cells .
Biomedical Research: MAD2 is extensively studied in cancer research due to its role in maintaining genomic stability. Its overexpression or underexpression is associated with various cancers, including gastric, liver, lung, and breast cancers .
Diagnostic Tools: Altered expression levels of MAD2 can serve as a diagnostic marker for certain cancers. Its expression patterns in cancerous tissues can provide insights into tumor progression and prognosis .
Therapeutic Strategies: Targeting MAD2 and its regulatory pathways offers potential therapeutic strategies for cancer treatment. Inhibitors of MAD2-Cdc20 interaction are being explored as potential anti-cancer agents .
Development to Aging and Disease: MAD2 plays a critical role throughout the cell cycle, particularly during mitosis. Its function in ensuring accurate chromosome segregation is vital for normal development and tissue homeostasis . Dysregulation of MAD2 can lead to aneuploidy and contribute to aging and age-related diseases, including cancer .