Cyclin B2 and p53 control proper timing of centrosome separation.

Abstract	Cyclins B1 and B2 are frequently elevated in human cancers and are associated with tumour aggressiveness and poor clinical outcome; however, whether and how B-type cyclins drive tumorigenesis is unknown. Here we show that cyclin B1 and B2 transgenic mice are highly prone to tumours, including tumour types where B-type cyclins serve as prognosticators. Cyclins B1 and B2 both induce aneuploidy when overexpressed but through distinct mechanisms, with cyclin B1 inhibiting separase activation, leading to anaphase bridges, and cyclin B2 triggering aurora-A-mediated Plk1 hyperactivation, resulting in accelerated centrosome separation and lagging chromosomes. Complementary experiments revealed that cyclin B2 and p53 act antagonistically to control aurora-A-mediated centrosome splitting and accurate chromosome segregation in normal cells. These data demonstrate a causative link between B-type cyclin overexpression and tumour pathophysiology, and uncover previously unknown functions of cyclin B2 and p53 in centrosome separation that may be perturbed in many human cancers.
Authors	Hyun-Ja Nam, Jan M van Deursen
Journal	Nature cell biology (Nat Cell Biol) Vol. 16 Issue 6 Pg. 538-49 (Jun 2014) ISSN: 1476-4679 [Electronic] England
PMID	24776885 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References	Ccnb1 protein, mouse Ccnb2 protein, mouse Cell Cycle Proteins Cyclin B1 Cyclin B2 Luminescent Proteins Proto-Oncogene Proteins Tumor Suppressor Protein p53 Aurka protein, mouse Aurora Kinase A Protein Serine-Threonine Kinases polo-like kinase 1 Separase
Topics	Aneuploidy Animals Aurora Kinase A (metabolism) Cell Cycle Proteins (metabolism) Cell Transformation, Neoplastic (genetics, metabolism, pathology) Cells, Cultured Centrosome (metabolism) Chromosome Aberrations Chromosome Segregation Cyclin B1 (deficiency, genetics) Cyclin B2 (deficiency, genetics, metabolism) Female Genes, APC Intestinal Neoplasms (genetics, metabolism, pathology) Luminescent Proteins (genetics, metabolism) Male Mice Mice, 129 Strain Mice, Inbred C57BL Mice, Transgenic Protein Serine-Threonine Kinases (metabolism) Proto-Oncogene Proteins (metabolism) RNA Interference Separase (metabolism) Signal Transduction Time Factors Transfection Tumor Suppressor Protein p53 (metabolism)

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