RESEARCH OF NOVEL COMPONENTS OF SONIC HEDGEHOG/GLI TRANSDUCTION PATHWAY

Sonic Hedgehog/GLI 传导途径新成分的研究

• 批准号: 7420731
• 负责人: GIANLUCA CANETTIERI
• 金额: $ 0.29万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-20 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7420731
• 关键词: Mammalia; cerebellum; granule cell; neoplastic growth; neoplastic transformation; pancreas; prostate; proteins; receptor; repression; skin; tissues

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Sonic hedgehog (Shh) is a secreted molecule that regulates the postnatal development of the cerebellum, by promoting the proliferation of granule cell precursors (GCPs). Shh binds the patched receptor and activates smoothened. This triggers a cascade of events that involves several cytoplasmic proteins (Fused, SUFU, PKA, Costal, GSK3) and culminates with the activation of the GLI trancription factors (GLI1, GLI2 and GLI3). Deregulation of the Shh pathway is linked to neoplastic transformation of several tissues, including cerebellum, pancreas, prostate and skin. Compounds that block Shh transduction pathway, such as cyclopamine, are suppressors of neoplastic growth in vitro and in vivo. Therefore, the complete knowledge of the mechanisms of activation and repression of Shh represents a key aspect to generate drugs able to suppress tumor growth.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。Sonic hedgehog（Shh）是一种分泌性分子，通过促进颗粒细胞前体（GCPs）的增殖来调节小脑的出生后发育。Shh结合补丁受体并激活smoothened。这触发了涉及几种细胞质蛋白（融合蛋白、SUFU、PKA、Costal、GSK 3）的级联反应，并以GLI转录因子（GLI 1、GLI 2和GLI 3）的激活而达到高潮。Shh通路的失调与几种组织的肿瘤转化有关，包括小脑、胰腺、前列腺和皮肤。阻断Shh转导途径的化合物，如环巴胺，是体外和体内肿瘤生长的抑制剂。因此，Shh的激活和抑制机制的完整知识代表了产生能够抑制肿瘤生长的药物的关键方面。