A novel role for high-mobility group a proteins in cellular senescence and heterochromatin formation

Narita, M., Narita, M., Krizhanovsky, V., Nunez, S., Chicas, A., Hearn, S. A., Myers, M. P., Lowe, S. W. (August 2006) A novel role for high-mobility group a proteins in cellular senescence and heterochromatin formation. Cell, 126 (3). pp. 503-14. ISSN 0092-8674 (Print)

URL: https://www.ncbi.nlm.nih.gov/pubmed/16901784
DOI: 10.1016/j.cell.2006.05.052

Abstract

Cellular senescence is a stable state of proliferative arrest that provides a barrier to malignant transformation and contributes to the antitumor activity of certain chemotherapies. Senescent cells can accumulate senescence-associated heterochromatic foci (SAHFs), which may provide a chromatin buffer that prevents activation of proliferation-associated genes by mitogenic transcription factors. Surprisingly, we show that the High-Mobility Group A (HMGA) proteins, which can promote tumorigenesis, accumulate on the chromatin of senescent fibroblasts and are essential structural components of SAHFs. HMGA proteins cooperate with the p16(INK4a) tumor suppressor to promote SAHF formation and proliferative arrest and stabilize senescence by contributing to the repression of proliferation-associated genes. These antiproliferative activities are canceled by coexpression of the HDM2 and CDK4 oncogenes, which are often coamplified with HMGA2 in human cancers. Our results identify a component of the senescence machinery that contributes to heterochromatin formation and imply that HMGA proteins also act in tumor suppressor networks.

Item Type: Paper
Uncontrolled Keywords: Animals Cell Aging genetics Cell Line Cell Nucleus genetics metabolism Cell Proliferation Cell Transformation Neoplastic genetics metabolism Cells Cultured Cyclin-Dependent Kinase 4 genetics metabolism Cyclin Dependent Kinase Inhibitor p16 genetics metabolism Gene Expression Regulation Neoplastic genetics HMGA Proteins genetics metabolism HMGA2 Protein genetics metabolism Heterochromatin genetics metabolism Humans Mice Proto-Oncogene Proteins c-mdm2 genetics metabolism Trans-Activation (Genetics)genetics Tumor Suppressor Proteins genetics metabolism
Subjects: diseases & disorders > cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > HMGA proteins
diseases & disorders > cancer > drugs and therapies
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > Chromatin dynamics > heterochromatin
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > senescence
CSHL Authors:
Communities: CSHL labs > Lowe lab
Depositing User: CSHL Librarian
Date: 11 August 2006
Date Deposited: 09 Dec 2011 16:55
Last Modified: 27 Apr 2018 14:22
Related URLs:
URI: http://repository.cshl.edu/id/eprint/22868

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving