Journal article

Targeting the centrosome and polo-like kinase 4 in osteosarcoma

Fergal C Kelleher, Jeska Kroes, Jeremy Lewin

CARCINOGENESIS | OXFORD UNIV PRESS | Published : 2019

Abstract

It has been historically uncertain if extra centrosomes are a cause or consequence of tumorigenesis. Experiments have recently established that overexpression of polo-like kinase 4 (PLK4) promotes centrosome amplification with consequential promotion of cellular aneuploidy. Furthermore, centrosome amplification drives spontaneous tumorigenesis in mice. Tissues lacking normal functional p53 tolerate extra centrosomes, whereas p53 proficient tissues initiate proliferative arrest in this circumstance. Extra centrosomes trigger activation of the multi-protein PIDDosome complex, with Caspase-2 effecting cleavage of the p53-negative regulator mouse double minute 2, consequent stabilization of p53 ..

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