An Optimal Range of Transcription Potency is Necessary for Efficient Cell Transformation by C-rel to Ensure Optimal Nuclear Localization and Gene-specific Activation.
From: Center for Advanced Biotechnology and Medicine, Robert Wood Johnson Medical School, Piscataway, NJ 08854-5638, USA.
Oncogene
- Publish Date: Jun 2007
- ISSN: 0950-9232
- Volume: 26
- Issue: 27
- Pages: 4038-43
- Medium: Print
- Language: English
- Citation (JAMA): Fan Y, Gélinas C, et al. An Optimal Range of Transcription Potency is Necessary for Efficient Cell Transformation by C-rel to Ensure Optimal Nuclear Localization and Gene-specific Activation.. Oncogene Jun 2007;26:4038-43
Abstract
c-Rel is overexpressed in several B-cell lymphomas and c-rel gene overexpression can transform primary chicken lymphoid cells and induce tumors in animals. Although c-Rel is generally a stronger transcriptional activator than its viral derivative v-Rel, its oncogenic activity is significantly weaker. Among the mutations acquired during c-Rel’s evolution into v-Rel are deletion of c-Rel’s transactivation domain 2 (cTAD2) and mutations in cTAD1. Given the critical role of the Rel TADs in cell transformation, we investigated how mutations in c-Rel’s cTAD1 and cTAD2 contribute to its oncogenicity and that of v-Rel. Mutations in cTAD2 noticeably increased c-Rel’s transforming activity by promoting its nuclear localization and gene-specific transactivation, despite an overall decrease in kappaB site-dependent transactivation potency. Conversely, substitution of vTAD by cTAD1 increased v-Rel’s transactivation and transforming efficiencies, whereas its substitution by the stronger cTAD2 compromised activation of mip-1beta but not irf-4 and was detrimental to cell transformation. These results suggest that the Rel TADs differentially contribute to gene-specific activation and that an optimal range of transcription potency is necessary for efficient transformation. These findings may have important implications for understanding how Rel TAD mutations can lead to a more oncogenic phenotype.
Mesh Headings (Keywords): Amino Acid Sequence, Animals, Binding Sites, Cell Nucleus, Cell Transformation, Neoplastic, Cells, Cultured, Chickens, Electrophoretic Mobility Shift Assay, Humans, Immunoprecipitation, Lymphocytes, Molecular Sequence Data, Mutation, Oncogene Proteins v-rel, Protein Binding, Proto-Oncogene Proteins c-rel, Trans-Activation (Genetics), Transcription, Genetic
Check for Full Text / PubMed Unique Identifier (PMID): 17173064
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