Exp Mol Med.  2003 Oct;35(5):448-453.

Impaired phosphorylation and mis-localization of Bub1 and BubR1 are responsible for the defective mitotic checkpoint function in Brca2-mutant thymic lymphomas

Affiliations
  • 1Division of Molecular Life Sciences, Ewha Womans University, 11-1 Daehyun-dong, Seodaemoon-gu, Seoul 120-750, Korea.

Abstract

Breast cancer susceptibility gene, BRCA2, is a tumor suppressor and individuals who inherit one defected copy of BRCA2 allele experience early onset breast cancer or ovarian cancer accompanied by the loss of the wild type allele. Mouse model for Brca2 mutation shows growth retardation and paradoxical occurrence of thymic lymphomas. Thymic lymphomas from Brca2-mutant mice harbor mutations in p53, Bub1, and BubR1, which function as mitotic checkpoint proteins. Therefore, interplay between Brca2 and mitotic checkpoint has been suggested in the maintenance of genetic fidelity, although it has not been assessed whether the unique mutations in Bub1 and BubR1 found in Brca2-mutant mice are responsible for the abolishment of mitotic checkpoint function. This report demonstrates that Bub1 and BubR1 mutant proteins from Brca2(-/-)thymic lymphomas have defects in the phosphorylation and kinetochore localization after spindle damage. Thus, the mutations of Bub1 and BubR1 found in Brca2- mutant mice indeed are responsible for the chromosome instability in Brca2-mutated tumors.


MeSH Terms

Animals
BRCA2 Protein/*genetics/*metabolism
Cell Cycle Proteins
Cell Transformation, Neoplastic/metabolism
Mice
*Mitosis
Mutation/*genetics
Phosphorylation
Protein Kinases/*metabolism
Protein Transport
Support, Non-U.S. Gov't
T-Lymphocytes/metabolism
Thymus Neoplasms/genetics/*pathology
Full Text Links
  • EMM
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr