TRANSFORMING GENES OF AVIAN RNA TUMOR VIRUSES

转化禽 RNA 肿瘤病毒的基因

• 批准号: 3916743
• 负责人: T S PAPAS
• 金额: --
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3916743
• 关键词: DNA directed DNA polymerase; Downs syndrome; Drosophilidae; RNA virus; Retroviridae; Retroviridae disease; Xenopus; avian leukosis virus; cats; clone cells; evolution; fish; gel electrophoresis; gene expression; genetic manipulation; genetic mapping; genetic transcription; genetic transduction; genome; human tissue; laboratory mouse; leukemia; molecular cloning; molecular oncology; molecular pathology; nucleic acid hybridization; nucleic acid probes; nucleic acid sequence; oncogenes; oncoproteins; protein sequence; protooncogene; saltwater environment; sea urchins; species difference; transforming virus; transposon /insertion element; viral leukemogenesis; virus DNA; virus genetics; virus replication

A major effort by the LMO has been to elucidate the processes by which specific retroviral oncogenes, as well as their cellular homologs, are able to impact on critical cellular events. Using the avian retroviral oncogenes, ets and myc, as probes, we have detected, isolated, cloned and sequenced the cellular homologs of these genes from evolutionarily diverse organisms such as humans, mice, fish, sea urchin, Xenopus and Drosophila. There is a family of these proto-ets genes where specific regions of these cellular genes are retained at very high levels of homology; each of these proto-ets oncogenes was compared to their viral homologs. In all cases, the proto-oncogenes were much larger than their corresponding viral oncogenes. The consistent truncation of the viral oncogene and consequent alteration of its products implicates this type of damage as a general event that results in the disruption of the function of these highly conserved genes. We have also developed and exploited several expression vector systems, both prokaryotic and eukaryotic, to produce oncogene- specific products in quantity. These expressed products were used to purify, characterize and develop immunologic reagents to locate and characterize the cellular proto-oncogene products. Such reagents have also been used to probe for the expression of oncogene-specific products in normal and malignant tissues and related them to specific human pathologies. We have been able to isolate and characterize the gene products of ets and determine some relevant properties of this gene that implicate its function in the signal transduction pathway and in T4 cell maturation. It also seems that these proto-ets genes may play a significant role in Down's syndrome (DS), and may possibly be related to the higher than normal incidence of leukemic disease seen in DS patients.

LMO的一项主要工作是通过