The dynamics of E1A in regulating networks and canonical pathways in quiescent cells
| Autor: | Mrinal K. Ghosh, Jennifer Bongorno, Jingfeng Sha, Keman Zhang, Jean-Eudes Dazard, Marian L. Harter, Linda Cai, Chien Ngoc Nguyen, Omar Yasin |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
DNA repair
Short Report lcsh:Medicine Biology 01 natural sciences General Biochemistry Genetics and Molecular Biology 010104 statistics & probability 03 medical and health sciences Viral life cycle Gene expression Gene silencing 0101 mathematics lcsh:Science (General) Gene lcsh:QH301-705.5 030304 developmental biology Medicine(all) Genetics 0303 health sciences Biochemistry Genetics and Molecular Biology(all) lcsh:R DNA replication General Medicine Cell cycle Cell biology lcsh:Biology (General) DNA microarray lcsh:Q1-390 |
| Zdroj: | BMC Research Notes, Vol 4, Iss 1, p 160 (2011) BMC Research Notes |
| ISSN: | 1756-0500 |
| Popis: | Background Adenoviruses force quiescent cells to re-enter the cell cycle to replicate their DNA, and for the most part, this is accomplished after they express the E1A protein immediately after infection. In this context, E1A is believed to inactivate cellular proteins (e.g., p130) that are known to be involved in the silencing of E2F-dependent genes that are required for cell cycle entry. However, the potential perturbation of these types of genes by E1A relative to their functions in regulatory networks and canonical pathways remains poorly understood. Findings We have used DNA microarrays analyzed with Bayesian ANOVA for microarray (BAM) to assess changes in gene expression after E1A alone was introduced into quiescent cells from a regulated promoter. Approximately 2,401 genes were significantly modulated by E1A, and of these, 385 and 1033 met the criteria for generating networks and functional and canonical pathway analysis respectively, as determined by using Ingenuity Pathway Analysis software. After focusing on the highest-ranking cellular processes and regulatory networks that were responsive to E1A in quiescent cells, we observed that many of the up-regulated genes were associated with DNA replication, the cell cycle and cellular compromise. We also identified a cadre of up regulated genes with no previous connection to E1A; including genes that encode components of global DNA repair systems and DNA damage checkpoints. Among the down-regulated genes, we found that many were involved in cell signalling, cell movement, and cellular proliferation. Remarkably, a subset of these was also associated with p53-independent apoptosis, and the putative suppression of this pathway may be necessary in the viral life cycle until sufficient progeny have been produced. Conclusions These studies have identified for the first time a large number of genes that are relevant to E1A's activities in promoting quiescent cells to re-enter the cell cycle in order to create an optimum environment for adenoviral replication. |
| Databáze: | OpenAIRE |
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