STIL基因的分子生物学特征及效应

Molecular characterization and biological effects of STIL gene

STIL基因是从急性T淋巴细胞白血病基因中克隆而来,作为一种癌基因,STIL与生物体内中心体的生成、复制及细胞有丝分裂密切相关。中心粒是细胞分裂的控制中心。STIL与PLK4(一种中心粒复制相关蛋白)在细胞分裂的G1期中期组成包含有卷曲螺旋结构域(coiled-coil domain,CCD)和STAN模体(STAN motif)的复合体参与中心粒的形成、复制,调控细胞有丝分裂,并且生成中心体的数量与STIL蛋白含量成正比。进一步的研究发现,在神经系统中STIL截断突变基因(STILT)通过影响中心粒的增殖从而导致小头畸形症(MCPH)的发生,并与全前脑畸形(HPE)的发病有关。增强STIL介导的Shh信号转导通路可以降低视网膜多巴胺能细胞对神经毒素的敏感性,从而保护视网膜。经研究发现,STIL在多种肿瘤组织均有表达,并通过调节中心体的结构和数目,影响染色体不稳定性形成参与恶性肿瘤发生、发展及转移。在肺癌特别是非小细胞肺癌中STIL呈过表达状态。在胰腺癌中,STIL在Hedgehog信号通路中通过与SUFU(融合抑制蛋白)和Gli(一种锌指蛋白)相互作用导致胰腺癌的发生。本篇综述旨在探讨STIL在中心粒复制和细胞增殖方面的作用,揭示其与神经系统疾病及恶性肿瘤发生的关系及潜在机制,为疾病的预后和治疗提供新的方向。

STIL gene, an oncogene,was cloned from the T-cell acute lymphoblastic leukemia. STIL is closely related with the formation and duplication of eentrioles and regulating cell mitosis in organism. Centriole is the center of cell mitosis. In cell mitosis, during the middle of G1 phase, STIL and PLK4 （a centriole proliferation protein） form a complex containing coiled-coil domain （CCD） and STAN motif which participating the formation of centrioles and regulating cell mitosis. Be- sides,the number of the formation of eentrioles is proportional to the content of STIL protein. Further studies indieate that in nervous system, STIL truncating mutations （STILT） mediate the development of MCPH（Mierocephaly） by affecting the duplication of centrioles. STIL is also related to HPE（ Holoprosencephaly）. Enhancing the Shh signal transduction pathway mediate by STIL, which could make retinal dopaminergic cells reduee the sensitivity to neurotoxin, so as to protect the retina. It turns out that STIL expressed in multiple tumor tissues. STIL participates the formation, progress and metastasis of malignant tumor by regulating the number and structure of centriole, promoting the performance of chromosome instability. STIL is overexpressed in lung cancer especially in non-small cell lung cancer. In pancreatic cancer, STIL interacts with SUFU and Gli in Hedgehog pathway to mediating the progress of tumor. In this review,we aim to discuss the function of STIL in centriole and cell proliferation, elaborating it＇ s association and potential mechanism in neurologic diseases and malignancies,providing a new direction of prognosis and treatment to the disease.