Hedgehog signaling plays an important role in the embryonic development and adult tissue homeostasis. Its misregulation will lead to many kinds of disease like cancer. Vertebrates have three transcriptional factors, Gli1, Gli2 and Gli3. Among them, Gli3 is a very special transcriptional factor which closely resembles Cubitus interruptus (Ci, in Drosophila) structurally and functionally as a ‘double agent’ for Sonic Hedgehog (Shh) target gene expression. However the specific regulation mechanism of Gli3 still elusive.
A team of scientists led by Prof. ZHAO Yun at the Institute of Biochemistry and Cell Biology (SIBCB), Institutions of Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), have identified Set7 mediated Gli3 methylation plays a positive role in the activation of Sonic Hedgehog pathway in mammal. Supervised by Prof. ZHAO Yun, FU Lin and colleagues identified a new Post-translational modifications (PTMs) of Gli3. They found that Gli3 full-length, but not the truncated repression form, can be methylated at K436 and K595, in vitro and in vivo. This methylation is specifically catalyzed by Set7, a lysine methyltransferase (KMT). Methylation at K436 and K595 respectively increases the stability and DNA binding ability of Gli3, resulting in an enhancement of Shh signaling activation. Furthermore, functional experiments indicate that the Set7 mediated Gli3 methylation contributes to the tumor growth and metastasis in non-small cell lung cancer (NSCLC) in vitro and in vivo.
This study entitled ‘Set7 mediated Gli3 methylation plays a positive role in the activation of Sonic Hedgehog pathway in mammal’ was published online by eLIFE on 5 May, 2016.
This work was supported by grants from the ‘Strategic Priority Research Program’ of the Chinese Academy of Sciences and the National Natural Science Foundation of China.
CONTACT:
ZHAO Yun, Principal Investigator, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Email: yunzhao@sibcb.ac.cn
Phone: +86-21-54921618
Figure 1. Set7 mediated methylation of Gli3 full length on K436 and K595 promote the tumor growth. (Image provided by Prof. ZHAO Yun’s lab)
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