Phosphorylation-mediated interaction between human E26 transcription factor 1 and specific protein 1 is required for tumor cell migration  

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作  者:Xianhui Wen Xingsheng Sun Zheyuan Ou Jun Jiang Qingmei Chen Xirong He Zhangsheng Hu Han Qiao Kuan Zhou Xin Li Yiqun Deng Jikai Wen 

机构地区:[1]Guangdong Provincial Key Laboratory of Protein Function and Regulation in Agricultural Organisms,College of Life Sciences,South China Agricultural University,Guangzhou 510642,China [2]Guangdong Laboratory for Lingnan Modern Agriculture,South China Agricultural University,Guangzhou 510642,China [3]Key Laboratory of Zoonosis of Ministry of Agriculture and Rural Affairs,South China Agricultural University,Guangzhou 510642,China

出  处:《Acta Biochimica et Biophysica Sinica》2022年第10期1441-1452,共12页生物化学与生物物理学报(英文版)

基  金:supported by the grants from the Joint Fund of the Department of Education of Guangdong Province(No.2018KZDXM015);the National Natural Science Foundation of China(No.31471234);the Special Funds for the Cultivation of Guangdong College Students′Scientific and Technological Innovation(“Climbing Program”,No.pdjh2020b0091).

摘  要:Transcription factors,human E26 transcription factor 1(Ets1)and specific protein 1(Sp1),are known to induce gene expression in tumorigenicity.High Ets1 expression is often associated with colorectal tumorigenesis.In this study,we discover that metastasis and clone formation in SW480 cells mainly depend on the direct interaction between Ets1 and Sp1 instead of high Ets1 expression.The interaction domains are further addressed to be the segment at Sp1(626-708)and the segment at Ets1(244-331).In addition,the phosphorylation inhibition of Ets1 at Tyr283 by either downregulation of Src kinase or Src family inhibitor treatment decreases the interaction between Sp1 and Ets1 and suppresses SW480 migration.Either administration or overexpression of the peptides harboring the interaction segment strongly inhibits the colony formation and migration of SW480 cells.Our findings suggest that the interaction between Ets1 and Sp1 rather than Ets1 alone promotes transformation in SW480 cells and provide new insight into the Ets1 and Sp1 interaction as an antitumour target in SW480 cells.

关 键 词:protein interactions ETS1 SP1 PP2 DASATINIB colon cancer 

分 类 号:R735.34[医药卫生—肿瘤]

 

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