MEMBRANE-BOUND RAS P21 REGULATION BY GAP AND LIPIDS

通过间隙和脂质调节膜结合 RAS P21

• 批准号: 3493117
• 负责人: STEPHEN B BOCCKINO
• 金额: $ 5万
• 依托单位: SPHINX PHARMACEUTICALS CORPORATION
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-30 至 1993-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3493117
• 关键词: Baculoviridae; binding proteins; bioassay; cell cycle; cytotoxicity; drug adverse effect; drug screening /evaluation; enzyme activity; enzyme mechanism; guanine nucleotide binding protein; guanosinetriphosphatases; intermolecular interaction; lipids; membrane proteins; method development; oncogenes; transfection /expression vector

DESCRIPTION (Adapted from applicant's abstract):The long-term goal of this project is to discover drugs that will protect normal cells from cancer chemotherapy. The oncogene ras is present in approximately 30 percent of human tumors: a normal non-oncogenic ras is found in normal cells. This normal ras (but not oncogenic ras) can be switched off by the cytosolic protein GAP resulting in inhibition of cell division. This difference can be exploited by compounds that act through GAP-ras to inhibit the proliferation of normal cells, sparing them from the effects of anti- proliferative therapy. Most previous work on GAP-ras interactions has utilized soluble ras. Since lipids appear to regulate the GAP-ras interaction, it is important to use the more physiological membrane-bound form of ras p21. In Phase I of this SBIR grant, an assay will be constructed for membrane-bound non- oncogenic ras protein and its regulation by GAP (Specific Aim 1). The membrane-bound ras will then be used to study the effects of regulatory lipids (Specific Aim 2). Subsequent to Phase I, compounds acting to inhibit normal ras function will be identified, and tested in relevant cell and animal models.

描述（改编自申请人的摘要）：本项目的长期目标 一个项目是发现保护正常细胞免受癌症侵害的药物 化疗 癌基因ras存在于大约30%的 人类肿瘤：在正常细胞中发现正常的非致癌Ras。 这 正常ras（但不是致癌ras）可以被细胞质中的 GAP蛋白导致细胞分裂抑制。 这种差异可以 被通过GAP-ras作用的化合物利用，以抑制 正常细胞的增殖，使它们免受抗- 增殖疗法 以前大多数关于GAP-ras相互作用的工作都利用了可溶性ras。 由于脂质似乎调节GAP-ras相互作用， 以使用Rasp21的更生理性的膜结合形式。 一期 在这项SBIR赠款中，将建立一种用于膜结合非- 癌基因ras蛋白及其由GAP（Specific Aim 1）调控。 的 膜结合ras将被用来研究调节性的作用。 脂质（具体目标2）。在阶段I之后，化合物作用于 抑制正常Ras功能将被鉴定，并在相关的 细胞和动物模型。