MAD1 Activators
MAD1, or Mitotic Arrest Deficient 1, serves as a critical component of the spindle assembly checkpoint (SAC), a surveillance mechanism that ensures accurate chromosome segregation during cell division. Functionally, MAD1 functions as a key mediator in the SAC by monitoring the attachment of spindle microtubules to kinetochores, specialized protein structures on chromosomes essential for proper chromosome alignment and segregation. Upon detection of unattached or improperly attached kinetochores, MAD1 undergoes conformational changes, leading to the recruitment and activation of other SAC components, including MAD2 and BUBR1. Through its interactions with these SAC proteins, MAD1 orchestrates the assembly of mitotic checkpoint complexes (MCCs), which inhibit the activity of the anaphase-promoting complex/cyclosome (APC/C), a ubiquitin ligase responsible for targeting key cell cycle regulators for degradation. By delaying the onset of anaphase until all chromosomes are properly aligned on the metaphase plate, MAD1 ensures the fidelity of chromosome segregation and curbs the accumulation of genomic instability, which is a hallmark of cancer.
Activation of MAD1 is tightly regulated by multiple mechanisms operating at both the transcriptional and post-translational levels. Transcriptional activation of MAD1 gene expression is controlled by cell cycle-dependent transcription factors and signaling pathways that regulate SAC activity in response to mitotic cues and DNA damage. Additionally, post-translational modifications, including phosphorylation and ubiquitination, modulate MAD1 activity and localization during mitosis. Phosphorylation of specific residues within MAD1 by kinases such as Aurora B and Mps1 regulates its interaction with other SAC components and kinetochores, thereby fine-tuning the timing and strength of SAC activation. Furthermore, ubiquitination-mediated degradation of MAD1 after SAC satisfaction contributes to checkpoint silencing and mitotic exit. The intricate regulatory mechanisms governing MAD1 activation ensure its precise coordination of the SAC, safeguarding genome integrity and preserving cell viability during cell division.
Items 1 to 10 of 12 total
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| Product Name | CAS # | Catalog # | QUANTITY | Price | Citations | RATING |
|---|---|---|---|---|---|---|
Okadaic Acid | 78111-17-8 | sc-3513 sc-3513A sc-3513B | 25 µg 100 µg 1 mg | $291.00 $530.00 $1800.00 | 78 | |
Okadaic Acid is a potent inhibitor of protein phosphatases 1 and 2A. By inhibiting these phosphatases, it can cause hyperphosphorylation of proteins involved in the spindle assembly checkpoint, which may lead to an increased recruitment and activation of MAD1. | ||||||
Taxol | 33069-62-4 | sc-201439D sc-201439 sc-201439A sc-201439E sc-201439B sc-201439C | 1 mg 5 mg 25 mg 100 mg 250 mg 1 g | $41.00 $74.00 $221.00 $247.00 $738.00 $1220.00 | 39 | |
Paclitaxel stabilizes microtubules and can inadvertently enhance the activity of the spindle assembly checkpoint, leading to the potential activation of MAD1 by preventing its turnover and ensuring its presence at the kinetochores. | ||||||
BI-D1870 | 501437-28-1 | sc-397022 sc-397022A | 1 mg 5 mg | $92.00 $260.00 | 12 | |
BI-D1870 is an inhibitor of RSK (p90 ribosomal S6 kinase), which through its kinase activity, may play a role in spindle checkpoint regulation. By inhibiting RSK, it might indirectly enhance the activation of MAD1. | ||||||
Calyculin A | 101932-71-2 | sc-24000 sc-24000A | 10 µg 100 µg | $163.00 $800.00 | 59 | |
Calyculin A is another inhibitor of protein phosphatase 1 and 2A. Similar to Okadaic Acid, its action may result in the phosphorylation of proteins that interact with MAD1, possibly leading to increased MAD1 activity within the spindle checkpoint. | ||||||
Bortezomib | 179324-69-7 | sc-217785 sc-217785A | 2.5 mg 25 mg | $135.00 $1085.00 | 115 | |
By inhibiting the proteasome, these compounds can prevent the degradation of cell cycle regulatory proteins, potentially leading to the accumulation and activation of MAD1 as part of the spindle assembly checkpoint. | ||||||
MLN 8054 | 869363-13-3 | sc-484828 | 5 mg | $398.00 | ||
MLN8054 is an Aurora kinase A inhibitor. Aurora A’s inhibition can disrupt normal spindle assembly and may promote the activation of spindle checkpoint proteins, including MAD1, to prevent progression to anaphase. | ||||||
PF 4708671 | 1255517-76-0 | sc-361288 sc-361288A | 10 mg 50 mg | $179.00 $700.00 | 9 | |
PF-4708671 is a selective inhibitor of p70 S6 kinase. Its inhibition may affect the spindle assembly checkpoint and could contribute to the activation of MAD1 through altered signaling cascades related to cell cycle control. | ||||||
UCN-01 | 112953-11-4 | sc-202376 | 500 µg | $251.00 | 10 | |
UCN-01 (7-hydroxystaurosporine) inhibits multiple protein kinases and influences cell cycle progression. This compound can enhance the activity of the spindle assembly checkpoint and may lead to the activation of MAD1 by affecting its upstream regulators. | ||||||
5-Iodotubercidin | 24386-93-4 | sc-3531 sc-3531A | 1 mg 5 mg | $153.00 $464.00 | 20 | |
5-Iodotubercidin is an adenosine kinase inhibitor that may increase the levels of adenosine, altering cell cycle progression. This alteration can lead to the activation of MAD1 through increased checkpoint signaling. | ||||||
SP600125 | 129-56-6 | sc-200635 sc-200635A | 10 mg 50 mg | $40.00 $150.00 | 257 | |
SP600125 is a JNK inhibitor which, by modulating JNK activity, may impact the spindle assembly checkpoint. This modulation could lead to the indirect activation of MAD1 by affecting the proteins that control its localization and function. | ||||||