Walleye Dermal Sarcoma Virus Accessory Protein Function

角膜白斑真皮肉瘤病毒辅助蛋白功能

• 批准号: 7048518
• 负责人: SANDRA L QUACKENBUSH
• 金额: $ 23.33万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-06-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7048518
• 关键词: Retroviridae; apoptosis; biological signal transduction; cell proliferation; host organism interaction; immunoprecipitation; mitochondria; protein structure function; sarcoma; tissue /cell culture; transcription factor; viral carcinogenesis; virus protein; virus related neoplasm /cancer

DESCRIPTION (provided by applicant): The piscine retroviruses and their associate neoplasias are new models of oncogenesis. Walleye dermal sarcomas are associated with the presence of a complex retrovirus, walleye dermal sarcoma virus (WDSV). These sarcomas naturally develop and regress making them unique in the study of tumor biology. Walleye dermal sarcoma is transmissible to walleye fingerlings. This transmission is efficient, and disease induction is rapid. Only cell-free homogenates from regressing tumors, not from developing tumors, can transmit disease. Viral-gene expression and proviral burden are also significantly different in developing vs. regressing tumors: Only low levels of spliced accessory gene transcripts are present during tumor development, whereas high levels of all viral transcripts and virus are found in regressing tumors. The accessory genes, named as open reading frames, a, b, and c, presumably function in WDSV biology. The product of orf a is a cyclin homologue or "retroviral cyclin?T. The products of orf b and orf c have no clear homologies. We hypothesize that the accessory proteins are oncogenic, control changes in virus expression, and induce tumor regression. Significant progress has been made in the characterization of both novel and precedented mechanisms involved in these processes. The goals of this proposal are to further characterize the functions of the WDSV accessory proteins in the control of general transcription factors, cell proliferation, and apoptosis. Work will proceed with full characterization of interacting cellular proteins and functional assays of transcription, signal transduction, and mitochondrial targeting. These studies will support the long-term objective of delineating general mechanisms of tumor induction and regression.

描述（由申请人提供）：Piscine逆转录病毒及其 副肿瘤是肿瘤发生的新模型。角膜白斑皮肤肉瘤是 与存在复杂逆转录病毒的存在有关 病毒（WDSV）。这些肉瘤自然会发展和退缩，使其独特 在肿瘤生物学研究中。 Walleye Dermal肉瘤可传播 角膜白斑。这种传播是有效的，疾病诱导是 迅速的。只有无细胞的匀浆反应肿瘤，而不是从发育中发育 肿瘤可以传播疾病。病毒式表达和前病毒负担是 在发展和回归肿瘤方面也有显着差异：只有低 肿瘤期间存在剪接的附件基因转录物的水平 开发，而所有病毒转录本和病毒的高水平 在消退的肿瘤中。配件基因，称为开放式阅读帧，A，B， 和C，大概在WDSV生物学中起作用。 ORF A的产物是细胞周期蛋白 同源物或“逆转录病毒细胞周期蛋白？t。ORF B和ORF C的产物没有 清晰的同源性。我们假设辅助蛋白是致癌的， 控制病毒表达的变化，并诱导肿瘤消退。重要的 在新颖和先例的表征方面取得了进展 这些过程涉及的机制。该提议的目标是 进一步表征了WDSV附件蛋白的功能 控制一般转录因子，细胞增殖和凋亡。 工作将进行相互作用的细胞蛋白的全面表征 和转录，信号转导和线粒体的功能测定法 定位。这些研究将支持描述的长期目标 肿瘤诱导和回归的一般机制。