SMO
小结
SMO是原癌基因，编码蛋白是一种G蛋白偶联受体，是hedgehog信号通路的保守信号转导，在正常胚胎和神经元发育以及肿瘤发生中起重要作用。SMO是七跨膜结构域蛋白，其与G蛋白偶联受体具有一些结构和功能相似性。SMO突变在散发性基底细胞癌和成神经管细胞瘤中检测到，并已在许多其他肿瘤类型中检测到。
Smoothened (SMO) is a conserved signal transducer of the hedgehog signaling pathway, playing important roles in normal embryonic and neuronal development as well as tumorigenesis. SMO is a seven-transmembrane domain protein bearing some structural and functional similarity to G-protein coupled receptors. SMO activity is normally inhibited by patched (PTCH1), an upstream component of the Hedgehog pathway, via poorly understood mechanisms. Binding of extracellular Hedgehog ligands to PTCH1 leads to consecutive activation of SMO, which in turn induces modifications of the downstream GLI transcription factors leading to their activation. Activating mutations in SMO lead to constitutive activation of GLI-mediated transcription of important oncogenic genes. Such mutations have been implicated in sporadic basal cell carcinoma and medulloblastoma and have been identified in many other tumor types. Recent efforts have been made to specifically target SMO. A distinct set of mutations in the ligand binding pocket of SMO, however, has been described to confer resistance to SMO inhibitors such as vismodegib and related cyclopamine drugs.