The Kinesin Protein Kif7 Is a Critical Regulator of Gli Transcription Factors in Mammalian Hedgehog Signaling

被引:169
作者
Cheung, Helen Oi-Lam [1 ,2 ]
Zhang, Xiaoyun [1 ]
Ribeiro, Ana [3 ]
Mo, Rong [1 ]
Makino, Shigeru [1 ]
Puviindran, Vijitha [1 ]
Lo Law, Kelvin King [1 ,2 ]
Briscoe, James [3 ]
Hui, Chi-chung [1 ,2 ]
机构
[1] Hosp Sick Children, Program Dev & Stem Cell Biol, Toronto, ON M5G 1L7, Canada
[2] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada
[3] Natl Inst Med Res, MRC, Div Dev Neurobiol, London NW7 1AA, England
基金
英国医学研究理事会;
关键词
CUBITUS-INTERRUPTUS; SUBCELLULAR-LOCALIZATION; COSTAL2; MOUSE; TRANSDUCTION; SUPPRESSOR; MECHANISMS; DROSOPHILA; REPRESSOR; GRADIENT;
D O I
10.1126/scisignal.2000405
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
From insects to humans, the Hedgehog (Hh) signaling pathway has conserved roles in embryonic development and tissue homeostasis. However, it has been suggested that the lack of mammalian equivalents of Costal2 (Cos2) contributes to a divergence between the mechanism of Drosophila and mammalian Hh signal transduction. Here, we challenge this view by showing that the kinesin protein Kif7 is a critical regulator of Hh signaling in mice. Similar to Cos2, Kif7 physically interacted with Gli transcription factors and controlled their proteolysis and stability, and acted both positively and negatively in Hh signaling. Thus, Kif7 is a missing component of the mammalian Hh signaling machinery, implying a greater commonality between the Drosophila and mammalian system than the prevailing view suggests.
引用
收藏
页数:7
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