Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.69 (APC)
 16,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Microtubule associated proteins are involved in regulation of microtubule dynamics. Its mutation and dysregulation result in severe consequences such as mitotic block and apoptosis. NuSAP has been reported as a microtubule associated protein, depletion of which by RNAi results in spindle deficiency and cytokinesis failure. However, its role in regulation of cell cycle and how NuSAP protein is controlled during cell cycle progression still remains unclear. Here we show that NuSAP can be ubiquitinated and degraded by APC/C-hCdh1 E3 ligase. Evolutionally conserved KEN box functions as the degron of NuSAP. Overexpression of NuSAP induces mitotic arrest and the microtubule associated domain and nuclear localization are both required for NuSAP to induce mitotic arrest. Furthermore, overexpression of NuSAP results in cells accumulation with microtubule bundling and spindle deficiency. Thus, our results give evidence for the first time that NuSAP protein level is tightly regulated by the APC/C ubiquitin ligase complex and NuSAP induces mitotic arrest dependent of its microtubule affinity.
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PMID:NuSAP is degraded by APC/C-Cdh1 and its overexpression results in mitotic arrest dependent of its microtubules' affinity. 1761 83

The ubiquitin ligase anaphase-promoting complex (APC/C) is essential for cell division in all eukaryotes. Loss of APC/C activity arrests cells at metaphase and results in severe aberrations of the mitotic spindle, but how the APC/C regulates spindle formation is not understood. Here, we report that the APC/C promotes the ubiquitination and degradation of four proteins required for Ran-dependent spindle assembly: Bard1, Hmmr, HURP, and NuSAP. Among these substrates, HURP and NuSAP can be degraded during spindle formation when the spindle checkpoint is active. Their degradation requires additional layers of regulation, and both SAFs are only degraded after being released from their inhibitor importin beta by Ran(GTP). Our findings reveal a tightly regulated mechanism by which the APC/C and the GTPase Ran control the abundance of active spindle assembly factors to achieve the accurate formation of the mitotic spindle.
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PMID:Regulated degradation of spindle assembly factors by the anaphase-promoting complex. 2047 43