TRANSFORMATION OF CELLS BY THE V-REL ONCOGENE

Re 1/-NF-κ B家族转录因子控制着细胞的生长 和脊椎动物淋巴样细胞的分化，以及突变体re 1 基因与许多淋巴癌有关， 动物和人类。 这项工作一直侧重于 了解Re 1的细胞和分子机制 转录因子影响细胞生长。 特别是 禽Rev-T的v-Re 1癌蛋白 逆转录病毒诱导恶性转化和永生化 禽淋巴样细胞，v-Re 1通过其在哺乳动物中具有毒性 细胞将被研究。具体而言，以下目标将 完成：将分离鸡re 1B cDNA， 将评估Re 1B与v-Re 1相互作用的能力; cDNA 编码蛋白质，可以相互作用，并调节 将鉴定对v-Re 1的C-末端序列的活性， 特征;抗凋亡蛋白对 将确定v-Re 1对细胞的永生化; v-Re 1突变体在哺乳动物成纤维细胞中诱导毒性， 确定;正如所说，将开发研究恶性 其他鸟类和哺乳动物Re 1蛋白在 鸟类和哺乳动物细胞;和细胞基因，其表达是 将鉴定Re 1转化细胞中通常改变的基因。 此外，某些Del蛋白激活的机制 转录将通过确定什么类型的 一般转录因子（如转录衔接子） v-Re1，c-Re1，Re1A， 和p85，在HUT 78人中发现的NF-κ B p100的致癌形式 白血病细胞 这些实验将作为模型 对于理解潜在的分子机制 人类淋巴恶性肿瘤的一个子集的发展。

The Re1/-NF-KB family of transcription factors controls the growth and differentiation of vertebrate lymphoid cells, and mutant re1 genes have been associated with a number of lymphoid cancers in animals and humans. This work has had a continuing focus on understanding the cellular and molecular mechanisms by which Re1 transcription factors affect cell growth. In particular, the mechanism by which the v-Re1 oncoprotein of the avian Rev-T retrovirus induces malignant transformation and immortalization of avian lymphoid cells, and by which v-Re1 is toxic in mammalian cells will be investigated. Specifically, the following aims will be accomplished: a chicken re1B cDNA will be isolated and the ability of Re1B to interact with v-Re1 will be assessed; cDNAs encoding proteins that can interact with and modulate the activities to C-terminal sequences of v-Re1 will be identified and characterized; the effect of anti-apoptosis proteins on immortalization of cells by v-Re1 will be determined; the ability of v-Re1 mutants to induce toxicity in mammalian fibroblasts will be determined; as says will be developed to study the malignant transforming potential of other avian and mammalian Re1 proteins in avian and mammalian cells; and cellular genes whose expression is commonly altered in Re1-transformed cells will be identified. Furthermore, the mechanism by which certain Del proteins activate transcription will be investigated by determining what types of general transcription factors (such as transcriptional adapters) are needed for transcriptional activation by v-Re1, c-Re1, Re1A, and p85, an oncogenic form of NF-KB p100 found in HUT78 human leukemia cells. Together, these experiments will serve as models for understanding the molecular mechanisms underlying the development of a subset of human lymphoid malignancies.