Dai Ping, Shinagawa Toshie, Nomura Teruaki, Harada Jun, Kaul Sunil C, Wadhwa Renu, Khan Md Matiullah, Akimaru Hiroshi, Sasaki Hiroshi, Colmenares Clemencia, Ishii Shunsuke
Laboratory of Molecular Genetics, RIKEN Tsukuba Institute, Ibaraki, Japan.
Genes Dev. 2002 Nov 15;16(22):2843-8. doi: 10.1101/gad.1017302.
Transcription factor Glioblastoma-3 (Gli3) is cleaved in the anterior region of the limb bud to generate its repressor form. In contrast, Sonic hedgehog (Shh) signaling from the posterior zone of polarizing activity blocks Gli3 processing and then induces the expression of Gli3 target genes, including Gli1. Here we report that the Ski corepressor binds to Gli3 and recruits the histone deacetylase complex. The Gli3-mediated repression was impaired by anti-Ski antibody and in Ski-deficient fibroblasts, and Shh-induced Gli1 gene transcription mediated by full-length Gli3 was inhibited by Ski. Furthermore, a Ski mutation enhanced the digit abnormalities caused by the Gli3 gene mutation. Thus, Ski plays an important role in pattern formation.
转录因子胶质母细胞瘤-3（Gli3）在肢芽前部区域被切割以产生其阻遏物形式。相比之下，来自极化活性后区的音猬因子（Shh）信号传导会阻断Gli3的加工过程，进而诱导包括Gli1在内的Gli3靶基因的表达。在此，我们报告Ski共抑制因子与Gli3结合并募集组蛋白去乙酰化酶复合体。抗Ski抗体以及在Ski缺陷型成纤维细胞中，Gli3介导的抑制作用均受到损害，并且Ski抑制了由全长Gli3介导的Shh诱导的Gli1基因转录。此外，Ski突变增强了由Gli3基因突变引起的指（趾）异常。因此，Ski在模式形成中发挥重要作用。
