Transgenic analyses of TGIF family proteins in Drosophila imply their role in cell growth

作     者：Yonghua Wang Lixia Wang Zhaohui Wang 

作者机构：Key Laboratory of Molecular and Developmental Biology Institute of Genetics and Developmental Biology Chinese AcademY of Sciences Beijing 100101 China Graduate School Chinese Academy of Sciences Beijing 100049 China 

出 版 物：《Journal of Genetics and Genomics》 (遗传学报（英文版）)

年 卷 期：2008年第35卷第8期

页      面：457-465页

核心收录：

学科分类：0710[理学-生物学] 07[理学] 071009[理学-细胞生物学] 09[农学] 0901[农学-作物学] 090102[农学-作物遗传育种] 

基　　金：the National Science Foundation of China (No. 305709) the National Basic Research Program of China (No. 2007CB947503) 

主　　题：TGIF cell size cell proliferation transgenic Drosophila melanogaster 

摘      要：TG-interacting factors （TGIFs） belong to a family of TALE-homeodomain proteins including TGIF, TGIF2, and TGIF2LX/Y （TGIF2 like on X or Y chromosome） in human. They potentially play important functions in various tissues during development. Mutations in TGIF are frequently associated with malformation of forebrain and facial structures; TGIF2 proteins are over-expressed in many ovarian cancer cell lines; and TGIF2LX/Y are specifically expressed in adult testis. The molecular functions of these proteins have been investigated mostly in cultured cells. TGIF and TGIF2 have been found as transcriptional repressors that modulate TGF-beta signaling. However these findings are far from sufficient to explain their mutant phenotypes or expression patterns, and the functions of TGIF2LX/Y have never been reported. Here we use Drosophila as a model system to explore the functions of TGIF family proteins in vivo. We observed in fly tissues such as fat body, epithelia, and neuronal cells, that expressing human TGIF2 or human TGIF2LX generally inhibited cell growth in size and number. Co-expressing Drosophila Myc, Cyclin E, or human c-MycS partially rescued the growth inhibition induced by human TGIFs, whereas activated insulin pathway signaling did not. Taken together, we provide in vivo evidence for the potential functions of human TGIF2 and TGIF2LX in growth control. Additionally, we confirmed that Drosophila TGIFs are transcriptional activators by assaying their activities in spermatogenesis.