Mechanism Of Bacp/Nlp Being Phosphorylated By Aurora B And Its Function In The Process Of Cytokinesis

Cytokinesis is the final but critical step of cell division by which the daughter cells are separated completely. Cytokinesis is such a complex process in which many molecules are involved. The aberrant process of cytokinesis could lead to malignant phenotype of cells.Bacp/Nlp (BRCA1 associated centrosomal protein/Ninein like protein) is a recently identified centrosomal protein which was found by our laboratory through yeast two hybrid approach using the C-terminal of BRCA1. It has been demonstrated to involve in the process of mitosis, including microtubule nucleation and spindle formation.In this study, we have found that Bacp/Nlp also contributes to regulation of cytokinesis. RNAi-mediated depletion of Bacp/Nlp could perturb the process of cytokinesis and then led to multinucleation. The modality of Bacp/Nlp involving in cytokinesis depends on its interaction with Aurora B in the final stage of mitosis. Inhibition of their interaction could lead to the failure of cytokinesis. Furthermore, we have identified Bacp/Nlp as the substrate of Aurora B. Phosphorylation of Bacp/Nlp by Aurora B acts in the final stage of cell division and affects the completion of cytokinesis. In addition, we mapped the special phsophorylating sites (Serl85, Ser448 and Ser585) of Bacp/Nlp, which have two different functions:first, phosphorylation on Ser448 and Ser585 is necessary for the localization of Bacp/Nlp in midbody; second, phosphorylation on Serl85 could stabilize Bacp/Nlp protein.Taken together, this study has explored one of the mechanisms for the role of Bacp/Nlp in the control of mitotic progression and demonstrated Aurora B regulation of Bacp/Nlp in the process of cytokinesis, providing novel insights into understanding on the process of cytokinesis.