Aurora B interaction of centrosomal Nlp regulates cytokinesis.
Cytokinesis is a fundamental cellular process, which ensures equal abscission and fosters diploid progenies. Aberrant cytokinesis may result in genomic instability and cell transformation. However, the underlying regulatory machinery of cytokinesis is largely undefined. Here, we demonstrate that Nlp (Ninein-like protein), a recently identified BRCA1-associated centrosomal protein that is required for centrosomes maturation at interphase and spindle formation in mitosis, also contributes to the accomplishment of cytokinesis. Through immunofluorescent analysis, Nlp is found to localize at midbody during cytokinesis. Depletion of endogenous Nlp triggers aborted division and subsequently leads to multinucleated phenotypes. Nlp can be recruited by Aurora B to the midbody apparatus via their physical association at the late stage of mitosis. Disruption of their interaction induces aborted cytokinesis. Importantly, Nlp is characterized as a novel substrate of Aurora B and can be phosphorylated by Aurora B. The specific phosphorylation sites are mapped at Ser-185, Ser-448, and Ser-585. The phosphorylation at Ser-448 and Ser-585 is likely required for Nlp association with Aurora B and localization at midbody. Meanwhile, the phosphorylation at Ser-185 is vital to Nlp protein stability. Disruptions of these phosphorylation sites abolish cytokinesis and lead to chromosomal instability. Collectively, these observations demonstrate that regulation of Nlp by Aurora B is critical for the completion of cytokinesis, providing novel insights into understanding the machinery of cell cycle progression.
Yan
Jie
J
State Key Laboratory of Molecular Oncology, Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Jin
Shunqian
S
Li
Jia
J
Zhan
Qimin
Q
D064107:Aurora Kinase B; D064127:Aurora Kinases; D018385:Centrosome / Q000378:metabolism*; D043171:Chromosomal Instability / Q000502:physiology; D048749:Cytokinesis / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
D008869:Microtubule-Associated Proteins; C476755:NINL protein, human; D009687:Nuclear Proteins; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases