Heterochromatin protein 1α: a hallmark of cell proliferation relevant to clinical oncology
| Autor: | Geneviève Almouzni, Leanne De Koning, Alexia Savignoni, Charlène Boumendil, Xavier Sastre-Garau, Bernard Asselain, Haniya Rehman |
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| Rok vydání: | 2009 |
| Předmět: |
Cell division
Chromosomal Proteins Non-Histone Heterochromatin proliferation Mitosis Breast Neoplasms Biology Humans cancer Gene silencing RNA Messenger Research Articles Cell Proliferation Regulation of gene expression HP1 Cell growth Carcinoma heterochromatin Cell cycle Chromatin Cell biology Gene Expression Regulation Chromobox Protein Homolog 5 Molecular Medicine Female cell cycle Heterochromatin protein 1 HeLa Cells |
| Zdroj: | EMBO Molecular Medicine |
| ISSN: | 1757-4684 1757-4676 |
| DOI: | 10.1002/emmm.200900022 |
| Popis: | Mammalian cells contain three closely related heterochromatin protein 1 (HP1) isoforms, HP1alpha, beta and gamma, which, by analogy to their unique counterpart in Schizosaccharomyces pombe, have been implicated in gene silencing, genome stability and chromosome segregation. However, the individual importance of each isoform during normal cell cycle and disease has remained an unresolved issue. Here, we reveal that HP1alpha shows a proliferation-dependent regulation, which neither HP1beta nor gamma display. During transient cell cycle exit, the HP1alpha mRNA and protein levels diminish. Transient depletion of HP1alpha, but not HP1beta or gamma, in tumoural and primary human cells leads to defects in chromosome segregation. Notably, analysis of an annotated collection of samples derived from carcinomas reveals an overexpression of HP1alpha mRNA and protein, which correlates with clinical data and disease outcome. Our results unveil a specific expression pattern for the HP1alpha isoform, suggesting a unique function related to cell division and tumour growth. The overexpression of HP1alpha constitutes a new example of a potential epigenetic contribution to tumourigenesis that is of clinical interest for cancer prognosis. |
| Databáze: | OpenAIRE |
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