Essential role for nuclear PTEN in maintaining chromosomal integrity Journal Article
| Authors: | Shen, W. H.; Balajee, A. S.; Wang, J.; Wu, H.; Eng, C.; Pandolfi, P. P.; Yin, Y. |
| Article Title: | Essential role for nuclear PTEN in maintaining chromosomal integrity |
| Abstract: | A broad spectrum of mutations in PTEN, encoding a lipid phosphatase that inactivates the P13-K/AKT pathway, is found associated with primary tumors. Some of these mutations occur outside the phosphatase domain, suggesting that additional activities of PTEN function in tumor suppression. We report a nuclear function for PTEN in controlling chromosomal integrity. Disruption of Pten leads to extensive centromere breakage and chromosomal translocations. PTEN was found localized at centromeres and physically associated with CENP-C, an integral component of the kinetochore. C-terminal PTEN mutants disrupt the association of PTEN with centromeres and cause centromeric instability. Furthermore, Pten null cells exhibit spontaneous DNA double-strand breaks (DSBs). We show that PTEN acts on chromatin and regulates expression of Rad51, which reduces the incidence of spontaneous DSBs. Our results demonstrate that PTEN plays a fundamental role in the maintenance of chromosomal stability through the physical interaction with centromeres and control of DNA repair. We propose that PTEN acts as a guardian of genome integrity. © 2007 Elsevier Inc. All rights reserved. |
| Keywords: | signal transduction; protein kinase b; controlled study; protein expression; unclassified drug; dna binding protein; gene mutation; nonhuman; mutant protein; protein domain; protein function; protein localization; protein analysis; animal cell; chromosome; mouse; animals; chromosomal proteins, non-histone; mice; dna repair; disease association; phosphatase; carboxy terminal sequence; embryo; lipid; protein binding; gene function; protein interaction; enzyme activity; dna strand breakage; cancer inhibition; double stranded dna; chromatin; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; protein transport; pten phosphohydrolase; fibroblasts; dna breaks, double-stranded; chromosomal instability; chromosome translocation; cell nucleus; mutant proteins; tumor; centromere; rad51 protein; functional proteomics; rad51 recombinase; chromosomes, mammalian; null cell; e2f1 transcription factor; protein cenp c |
| Journal Title: | Cell |
| Volume: | 128 |
| Issue: | 1 |
| ISSN: | 0092-8674 |
| Publisher: | Cell Press |
| Date Published: | 2007-01-12 |
| Start Page: | 157 |
| End Page: | 170 |
| Language: | English |
| DOI: | 10.1016/j.cell.2006.11.042 |
| PUBMED: | 17218262 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 194" - "Export Date: 17 November 2011" - "CODEN: CELLB" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
Related MSK Work