NuSAP is degraded by APC/C-Cdh1 and its overexpression results in mitotic arrest dependent of its microtubules' affinity.
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.
Li
Lu
L
State Key Laboratory of Proteomics, Department of Genomics and Proteomics, Beijing Institute of Radiation Medicine, Beijing Proteome Research Center, 27 Taiping Road, Beijing 100850, China.
Zhou
Ying
Y
Sun
Libo
L
Xing
Guichun
G
Tian
Chunyan
C
Sun
Jing
J
Zhang
Lingqiang
L
He
Fuchu
F
D020816:Amino Acid Motifs; D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism / Q000648:ultrastructure; D008938:Mitosis; D011123:Polyploidy; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism*
D008869:Microtubule-Associated Proteins; C000709213:NUSAP1 protein, human; D016159:Tumor Suppressor Protein p53; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome