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SL3-3 enhancer factor 1 transcriptional activators are required for tumor formation by SL3-3 murine leukemia virus
1Department of Applied Cell and Molecular Biology, University of Umeå, Sweden.
Abstract:
The transcriptional enhancers of retroviruses that lack an oncogene are important determinants of their oncogenicity. However, no specific cellular transcriptional activator has yet been found to determine the oncogenicity for any of these viruses. The SL3-3 enhancer factor 1 (SEF1) cellular transcriptional activators are expressed preferentially in T lymphocytes. In the SL3-3 murine leukemia virus enhancer, two different sequences can bind SEF1 activators. We show that mutation of the SEF1 binding sites disrupts the disease potential of SL3-3 murine leukemia virus, implying that SEF1 transcriptional activators are required for tumor induction by SL3-3. The SEF1 site mutations did not appear to affect the pathogenicity of SL3-3 by impairment of virus multiplication, but rather by a specific defect in the ability of neoplastic transformation.
Insights
Specific cellular transcriptional activators, SL3-3 enhancer factor 1 (SEF1), are crucial for the oncogenicity of SL3-3 murine leukemia virus. Disrupting SEF1 binding sites impairs tumor induction by affecting neoplastic transformation, not virus multiplication.
Area of Science:
- * Molecular biology
- * Virology
- * Oncology
Background:
- * Retroviral transcriptional enhancers lacking oncogenes are key to their oncogenic potential.
- * The specific cellular transcriptional activators driving this oncogenicity remain largely unidentified.
- * SL3-3 enhancer factor 1 (SEF1) activators are preferentially expressed in T lymphocytes.
Purpose of the Study:
- * To identify the specific cellular transcriptional activator determining the oncogenicity of SL3-3 murine leukemia virus.
- * To investigate the role of SEF1 binding sites within the SL3-3 enhancer in viral oncogenesis.
- * To elucidate the mechanism by which SEF1 influences tumor induction.
Main Methods:
- * Analysis of SEF1 activator binding sites within the SL3-3 murine leukemia virus enhancer.
- * Site-directed mutagenesis of SEF1 binding sequences in the viral enhancer.
- * Assessment of viral oncogenicity, tumor induction potential, and virus multiplication in mutated viral constructs.
Main Results:
- * Two distinct sequences within the SL3-3 enhancer were identified as binding sites for SEF1 activators.
- * Mutation of these SEF1 binding sites significantly disrupted the disease potential of SL3-3 murine leukemia virus.
- * The observed defect was specifically related to neoplastic transformation, with no significant impact on virus multiplication.
Conclusions:
- * SEF1 transcriptional activators are essential for tumor induction by SL3-3 murine leukemia virus.
- * The oncogenicity of SL3-3 virus is mediated through the interaction of SEF1 with its binding sites in the viral enhancer.
- * SEF1 plays a critical role in the neoplastic transformation process driven by SL3-3 virus.