The Aurora kinases: Role in cell transformation and tumorigenesis

Hiroshi Katayama, William R. Brinkley, Subrata Sen

Research output: Contribution to journalArticle

344 Citations (Scopus)

Abstract

Aurora kinases representing a novel family of serine/threonine kinases have been identified as key regulators of the mitotic cell division process. The three members of this kinase family, identified so far, referred to as Aurora-A, Aurora-B and Aurora-C kinases, are close homologues of the prototypic yeast Ipl1 and Drosophila aurora kinases, which are known to be involved in the regulation of centrosome function, bipolar spindle assembly and chromosome segregation processes. All three members of the mammalian kinase family have a catalytic domain that is highly conserved with a short C-terminal domain and an N-terminal domain of varying sizes. Following their discovery about five years ago, extensive research has focused on understanding the biological roles of these kinases and elucidation of their pathways, which regulate cell proliferation and maintenance of normal cellular phenotypes. Significant interest in the subject was generated since all three Aurora kinases family members were reported to be overexpressed in many human cancers, and elevated expression has been correlated with chromosomal instability and clinically aggressive disease in some instances. Ectopic overexpression of one member of the family, Aurora-A, was shown to induce oncogenic transformation in cells. Unlike most other putative oncogenes identified, so far, members of this kinase family are expressed and active at the highest level during G2-M phase of the cell cycle. Aurora kinases are localized at the centrosomes of interphase cells, at the poles of the bipolar spindle and in the midbody of the mitotic apparatus. Substrates identified for the Aurora-A and Aurora-B kinases, include a kinesin-like motor protein, spindle apparatus proteins, histone H3 protein, kinetochore protein and the tumor suppressor protein p53. Identification of Aurora kinases as RasGAP Src homology 3 domain binding protein, also implicates these kinases as potential effectors in the Ras pathway relevant to oncogenesis. Abnormal elevated expression of Aurora kinases detected in human cancer cells could help explain the underlying biological mechanisms responsible for the development of many cellular phenotypes associated with malignant cells. Identification of these mechanisms offers the possibility of designing novel targeted therapies for cancer in the future.

Original languageEnglish
Pages (from-to)451-464
Number of pages14
JournalCancer and Metastasis Reviews
Volume22
Issue number4
DOIs
Publication statusPublished - Dec 2003
Externally publishedYes

Fingerprint

Aurora Kinases
Carcinogenesis
Phosphotransferases
Centrosome
Spindle Apparatus
Cell Division
Aurora Kinase C
Proteins
Aurora Kinase B
Spindle Poles
Phenotype
Tumor Suppressor Protein p53
Kinetochores
Kinesin
Neoplasms
Chromosomal Instability
Chromosome Segregation
src Homology Domains
G2 Phase
Protein-Serine-Threonine Kinases

Keywords

  • Centrosome/microtubule organizing center
  • Chromosome instability
  • Cytokinesis
  • Kinetochore
  • Mitosis
  • Tumorigenesis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

The Aurora kinases : Role in cell transformation and tumorigenesis. / Katayama, Hiroshi; Brinkley, William R.; Sen, Subrata.

In: Cancer and Metastasis Reviews, Vol. 22, No. 4, 12.2003, p. 451-464.

Research output: Contribution to journalArticle

Katayama, Hiroshi ; Brinkley, William R. ; Sen, Subrata. / The Aurora kinases : Role in cell transformation and tumorigenesis. In: Cancer and Metastasis Reviews. 2003 ; Vol. 22, No. 4. pp. 451-464.
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