The Human RNA Polymerase II-Associated Factor 1 (hPaf1): A New Regulator of Cell-Cycle Progression
| Autor: | Michael A. Hollingsworth, Christophe Nemos, Surinder K. Batra, Nicolas Moniaux, Shonali Deb, Irena Dornreiter, Bing Zhu |
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| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Transcription
Genetic lcsh:Medicine RNA polymerase II Spindle Apparatus Biology Biochemistry Microtubules Models Biological 03 medical and health sciences 0302 clinical medicine Transcription (biology) Cell Line Tumor Gene expression Humans lcsh:Science Metaphase Transcription factor Mitosis 030304 developmental biology Regulation of gene expression Cell Nucleus Centrosome 0303 health sciences Cyclin-dependent kinase 1 Multidisciplinary lcsh:R Cell Cycle Nuclear Proteins Cell Biology Molecular biology Cell biology Gene Expression Regulation Neoplastic Oncology 030220 oncology & carcinogenesis biology.protein Disease Progression lcsh:Q Anaphase Research Article Transcription Factors |
| Zdroj: | PLoS ONE PLoS ONE, Vol 4, Iss 9, p e7077 (2009) |
| ISSN: | 1932-6203 |
| Popis: | Background: The human PAF (hPAF) complex is part of the RNA polymerase II transcription apparatus and regulates multiple steps in gene expression. Further, the yeast homolog of hPaf1 has a role in regulating the expression of a subset of genes involved in the cell-cycle. We therefore investigated the role of hPaf1 during progression of the cell-cycle. Methodology/Findings: Herein, we report that the expression of hPaf1, a subunit of the hPAF complex, increases with cellcycle progression and is regulated in a cell-cycle dependant manner. hPaf1 specifically regulates a subclass of genes directly implicated in cell-cycle progression during G1/S, S/G2, and G2/M. In prophase, hPaf1 aligns in filament-like structures, whereas in metaphase it is present within the pole forming a crown-like structure, surrounding the centrosomes. Moreover, hPaf1 is degraded during the metaphase to anaphase transition. In the nucleus, hPaf1 regulates the expression of cyclins A1, A2, D1, E1, B1, and Cdk1. In addition, expression of hPaf1 delays DNA replication but favors the G2/M transition, in part through microtubule assembly and mitotic spindle formation. Conclusion/Significance: Our results identify hPaf1 and the hPAF complex as key regulators of cell-cycle progression. Mutation or loss of stoichiometry of at least one of the members may potentially lead to cancer development. |
| Databáze: | OpenAIRE |
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