Piret Michelson;Priit Kogerman;Torben Osterlund;Alla Maloverjan;Marko Piirsoo
发明人:
Priit Kogerman,Alla Maloverjan,Marko Piirsoo,Piret Michelson,Torben Osterlund
申请号：
US13500902
公开号：
US20130040894A1
申请日:
2010.10.06
申请国别(地区):
US
年份:
2013
代理人:
摘要：
The present invention relates to human serine/threonine kinase ULK3 and its ability to regulate GLI transcription factors； mediators of SHH signaling. This disclosure demonstrates that ULK3 enhances endogenous and over-expressed GLI1 and GLI2 transcriptional activity in cultured cells, and ULK3 alters subcellular localization of GLI1. According to this disclosure ULK3 is an autophosphorylated kinase and phosphorylates GLI proteins in vitro. A peptide sequence in GLI1 C-terminus that is phosphorylated by ULK3 is provided in this disclosure. ULK3 catalytical activity is shown to be crucial for its function in SHH pathway. This disclosure shows that serine/threonine kinase ULK3 is involved in the SHH pathway as a positive regulator of GLI proteins. Furthermore, a therapeutic method in SHH dependent human disorders is disclosed by pharmacological inhibition of ULK3 kinase activity. Identification of ULK3 substrate sequence in GLI1 allows the design of peptide-based modulators of its kinase activity.
