The centrosome in normal and transformed cells.
The centrosome is a unique organelle that functions as the microtubule organizing center in most animal cells. During cell division, the centrosomes form the poles of the bipolar mitotic spindle. In addition, the centrosomes are also needed for cytokinesis. Each mammalian somatic cell typically contains one centrosome, which is duplicated in coordination with DNA replication. Just like the chromosomes, the centrosome is precisely reproduced once and only once during each cell cycle. However, it remains a mystery how this protein-based structure undergoes accurate duplication in a semiconservative manner. Intriguingly, amplification of the centrosome has been found in numerous forms of cancers. Cells with multiple centrosomes tend to form multipolar spindles, which result in abnormal chromosome segregation during mitosis. It has therefore been postulated that centrosome aberration may compromise the fidelity of cell division and cause chromosome instability. Here we review the current understanding of how the centrosome is assembled and duplicated. We also discuss the possible mechanisms by which centrosome abnormality contributes to the development of malignant phenotype.
Wang
Qiang
Q
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA. greene@reo.med.upenn.edu
Hirohashi
Yoshihiko
Y
Furuuchi
Keiji
K
Zhao
Huiwu
H
Liu
Qingdu
Q
Zhang
Hongtao
H
Murali
Ramachandran
R
Berezov
Alan
A
Du
Xiulian
X
Li
Bin
B
Greene
Mark I
MI
D000782:Aneuploidy; D064127:Aurora Kinases; D042846:CDC2-CDC28 Kinases / Q000502:physiology; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D018385:Centrosome / Q000502:physiology*; D043171:Chromosomal Instability / Q000502:physiology; D051357:Cyclin-Dependent Kinase 2; D004261:DNA Replication / Q000502:physiology; D008938:Mitosis / Q000502:physiology*; D008954:Models, Biological; D017346:Protein Serine-Threonine Kinases; D017027:Protein Tyrosine Phosphatases; D029701:Saccharomyces cerevisiae Proteins; D008941:Spindle Apparatus / Q000502:physiology*
C074860:CDC14 protein, S cerevisiae; D018797:Cell Cycle Proteins; D029701:Saccharomyces cerevisiae Proteins; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; D051357:Cyclin-Dependent Kinase 2; D017027:Protein Tyrosine Phosphatases