Hedgehog通路信号转导机制的研究进展

Progress on Hedgehog signaling transduction

Hedgehog(Hh)信号通路在胚胎的生长发育和形态发生过程中发挥了重要作用。该信号通路的活性异常不仅会引起发育异常,还会增加肿瘤发生率。本文详细论述了Hh信号通路各成员,重点阐述哺乳动物中Hh信号蛋白通过调控其下游Patched(Ptch)、Smoothened(Smo)、Suppressor of fused(Sufu)等各个成员实现对转录因子Gli调控作用的过程,即所谓的"经典信号转导途径"。这一信号转导途径在各物种中高度进化保守,而细胞器原纤毛(primary cilia)在此过程中发挥了类似"信号中心"的重要作用。此外,近年来大量研究显示,Hh信号还能通过非Gli依赖的"非经典信号转导途径"进行传导。它又可被细分为2种:(1)非Smo依赖的转导途径;(2)Smo依赖,非Gli依赖的转导途径。本文围绕Hh的经典、非经典信号转导途径的研究新进展作一综述。

Hedgehog （Hh） signaling pathway plays an important role during embryonic development and pattern formation. Disrup- tion of Hh pathway results in various developmental disorders and increasing cancer incidence. Here we provide a comprehensive review of the pathway members, focusing on how mammalian Hh regulates the Gli family of transcription factors through its down- stream members, the so-called ＂canonical signaling pathway＂. Hh signaling pathway is highly conserved among species, and primary cilia plays an important role as a ＂signaling center＂ during vertebrate signal transduction. Further, in the past few years, numerous studies have shown that Hh signal can also be transduced through Gli-independent ways collectively referred to as ＂non-canonical signaling pathways＂, which can be subdivided into two modules： （i） those not requiring Smo and （ii） those downstream of Smo that do not require Gli transcription factors. Thus, we review the rapid progress on canonical and non-canonical Hh pathways.