title: The role of centrosomal Nlp in the control of mitotic progression and tumourigenesis.
abstract: The human centrosomal ninein-like protein (Nlp) is a new member of the γ-tubulin complexes binding proteins (GTBPs) that is essential for proper execution of various mitotic events. The primary function of Nlp is to promote microtubule nucleation that contributes to centrosome maturation, spindle formation and chromosome segregation. Its subcellular localisation and protein stability are regulated by several crucial mitotic kinases, such as Plk1, Nek2, Cdc2 and Aurora B. Several lines of evidence have linked Nlp to human cancer. Deregulation of Nlp in cell models results in aberrant spindle, chromosomal missegregation and multinulei, and induces chromosomal instability and renders cells tumourigenic. Overexpression of Nlp induces anchorage-independent growth and immortalised primary cell transformation. In addition, we first demonstrate that the expression of Nlp is elevated primarily due to NLP gene amplification in human breast cancer and lung carcinoma. Consistently, transgenic mice overexpressing Nlp display spontaneous tumours in breast, ovary and testicle, and show rapid onset of radiation-induced lymphoma, indicating that Nlp is involved in tumourigenesis. This review summarises our current knowledge of physiological roles of Nlp, with an emphasis on its potentials in tumourigenesis.
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: Q
authors.initials: Q
authors.lastname: Zhan
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology*; D018385:Centrosome / Q000502:physiology*; D018450:Disease Progression; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008938:Mitosis / Q000502:physiology*; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D008869:Microtubule-Associated Proteins; C476755:NINL protein, human; D009687:Nuclear Proteins