Fructose-1,6-bisphosphatase 1 dephosphorylates IκBα and suppresses colorectal tumorigenesis
Fructose-1,6-bisphosphatase 1 dephosphorylates IκBα and suppresses colorectal tumorigenesis
复制标题
果糖-1,6-双磷酸酶 1 使 IγBα 去磷酸化并抑制结直肠肿瘤发生
DOI：
10.1038/s41422-022-00773-0
复制
发表时间：
2023-01
期刊：
影响因子：
44.1
通讯作者：
Yang Weiwei
中科院分区：
文献类型：
--
作者：
Zhu Wencheng;Chu Huiying;Zhang Yajuan;Luo Tianhang;Yu Hua;Zhu Hongwen;Liu Ye;Gao Hong;Zhao Yun;Li Quanlin;Wang Xiongjun;Li Guohui;Yang Weiwei
新出现的证据表明，一些使可溶性代谢物磷酸化的代谢酶也能作为蛋白激酶使多种蛋白质底物磷酸化，从而调节细胞周期、细胞凋亡以及许多其他基本的细胞过程。（最后一个“Ho”看起来是不完整的内容，如果还有遗漏信息，请补充完整后再次提问。）
Emerging evidence demonstrates that some metabolic enzymes that phosphorylate soluble metabolites can also phosphorylate a variety of protein substrates as protein kinases to regulate cell cycle, apoptosis and many other fundamental cellular processes. However, whether a metabolic enzyme dephosphorylates protein as a protein phosphatase remains unknown. Here we reveal the gluconeogenic enzyme fructose 1,6-biphosphatase 1 (FBP1) that catalyzes the hydrolysis of fructose 1,6-bisphosphate (F-1,6-BP) to fructose 6-phosphate (F-6-P) as a protein phosphatase by performing a high-throughput screening of metabolic phosphatases with molecular docking followed by molecular dynamics (MD) simulations. Moreover, we identify IκBα as the substrate of FBP1-mediated dephosphorylation by performing phosphoproteomic analysis. Mechanistically, FBP1 directly interacts with and dephosphorylates the serine (S) 32/36 of IκBα upon TNFα stimulation, thereby inhibiting NF-κB activation. MD simulations indicate that the catalytic mechanism of FBP1-mediated IκBα dephosphorylation is similar to F-1,6-BP dephosphorylation, except for higher energetic barriers for IκBα dephosphorylation. Functionally, FBP1-dependent NF-κB inactivation suppresses colorectal tumorigenesis by sensitizing tumor cells to inflammatory stresses and preventing the mobilization of myeloid-derived suppressor cells. Our finding reveals a previously unrecognized role of FBP1 as a protein phosphatase and establishes the critical role of FBP1-mediated IκBα dephosphorylation in colorectal tumorigenesis.
登录
查看更多内容
影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
影响因子：
100.3
作者：
Qiutang Li;I. Verma
通讯作者：
Qiutang Li;I. Verma
DOI：
--
发表时间：
2002
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Qiutang Li;I. Verma
通讯作者：
Qiutang Li;I. Verma
影响因子：
5.5
作者：
Roe, Daniel R.;Cheatham, Thomas E., III
通讯作者：
Cheatham, Thomas E., III
DOI：
10.1046/j.1432-1327.2000.01818.x
发表时间：
2000-12-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Nakai, Y;Irie, S;Sato, TA
通讯作者：
Sato, TA