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The role of centrosomal Nlp in the control of mitotic progression and tumourigenesis.

Li J, Zhan Q - Br. J. Cancer (2011)

Bottom Line: 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.This review summarises our current knowledge of physiological roles of Nlp, with an emphasis on its potentials in tumourigenesis.

View Article: PubMed Central - PubMed

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.

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.

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Cell-cycle functions and localisations of Nlp. Nlp associates with multiple structures at multiple stages of cell division. DNA/chromosomes are marked in blue, microtubules in black line and centrosomes in a pair of cylinders (red one represents mother centriole, and bright yellow one, daughter centriole). The blue circles are used to indicate the association of Nlp with different structures.
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fig1: Cell-cycle functions and localisations of Nlp. Nlp associates with multiple structures at multiple stages of cell division. DNA/chromosomes are marked in blue, microtubules in black line and centrosomes in a pair of cylinders (red one represents mother centriole, and bright yellow one, daughter centriole). The blue circles are used to indicate the association of Nlp with different structures.

Mentions: In mammalian cells, Nlp (also named as Nlp isoform A by van Wijk et al) is expressed in a cell-cycle-dependent manner with a peak at G2/M transition. Its subcellular localisation undergoes dynamic changes during mitosis. Further analysis suggests that Nlp, with a relatively short half-life, is able to be ubiquitinated and degraded via APC/C pathway (Wang and Zhan, 2007). The fluctuating expression and localisation patterns suggest that Nlp is temporally and spatially involves in various mitotic events, such as centrosome maturation, spindle formation and cytokinesis (Casenghi et al, 2003, 2005; Rapley et al, 2005; Yan et al, 2010) (Figure 1).


The role of centrosomal Nlp in the control of mitotic progression and tumourigenesis.

Li J, Zhan Q - Br. J. Cancer (2011)

Cell-cycle functions and localisations of Nlp. Nlp associates with multiple structures at multiple stages of cell division. DNA/chromosomes are marked in blue, microtubules in black line and centrosomes in a pair of cylinders (red one represents mother centriole, and bright yellow one, daughter centriole). The blue circles are used to indicate the association of Nlp with different structures.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3101908&req=5

fig1: Cell-cycle functions and localisations of Nlp. Nlp associates with multiple structures at multiple stages of cell division. DNA/chromosomes are marked in blue, microtubules in black line and centrosomes in a pair of cylinders (red one represents mother centriole, and bright yellow one, daughter centriole). The blue circles are used to indicate the association of Nlp with different structures.
Mentions: In mammalian cells, Nlp (also named as Nlp isoform A by van Wijk et al) is expressed in a cell-cycle-dependent manner with a peak at G2/M transition. Its subcellular localisation undergoes dynamic changes during mitosis. Further analysis suggests that Nlp, with a relatively short half-life, is able to be ubiquitinated and degraded via APC/C pathway (Wang and Zhan, 2007). The fluctuating expression and localisation patterns suggest that Nlp is temporally and spatially involves in various mitotic events, such as centrosome maturation, spindle formation and cytokinesis (Casenghi et al, 2003, 2005; Rapley et al, 2005; Yan et al, 2010) (Figure 1).

Bottom Line: 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.This review summarises our current knowledge of physiological roles of Nlp, with an emphasis on its potentials in tumourigenesis.

View Article: PubMed Central - PubMed

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.

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.

Show MeSH
Related in: MedlinePlus