Hedgehog signaling and signal transduction

描述(由申请人提供)：Hedgehog信号与许多癌症有关，并已被证明是抗癌治疗的有用靶点。之前的工作，包括我实验室的关键贡献，已经确定刺猬蛋白是动物发育的主要调节因子之一，在无脊椎动物和脊椎动物的大多数组织和器官中都发挥着关键作用。使用新开发的试剂和方法为研究HH信号开辟了新的途径，本申请中提出的工作将识别和表征HH产生细胞用来准备和传递HH蛋白的过程，HH接收细胞用来准备和处理HH到达的过程，以及调节Ci的形式和活性的过程，Ci是负责HH途径输出的转录因子。这些问题对于理解如何开发控制HH活性的新的更好的治疗方案至关重要。

DESCRIPTION (provided by applicant): Hedgehog signaling has been implicated in many cancers and has been shown to be a useful target for anti-cancer therapy. Previous work, including key contributions from my lab, have established that the Hedgehog protein is one of the major regulators of animal development, playing key roles in most tissues and organs in both invertebrates and vertebrates. Using newly developed reagents and methods that open new ways to study Hh signaling, the work proposed in this application will identify and characterize the processes that Hh-producing cells use to prepare and deliver Hh protein, the processes that Hh-receiving cells use to prepare for and handle its arrival, and the processes that regulate the form and activity of Ci, the transcription factor that is responsible for Hh pathway output. These issues are critical to understanding how new and better therapeutic regimens controlling Hh activity can be developed.