Cov pov thawj tshwm sim qhia tias qee qhov ntawm cov enzymes metabolic uas ua rau cov phosphorylation ntawm cov metabolites tuaj yeem ua cov protein kinases rau phosphorylate ntau cov protein substrates, yog li tswj lub voj voog ntawm tes, apoptosis, thiab ntau lwm cov txheej txheem ntawm tes. Txawm li cas los xij, me ntsis paub txog seb cov enzymes metabolic tuaj yeem ua raws li dephosphorylated protein phosphatase proteins.
Yang Weiwei Research Group ntawm Tuam Tshoj Center rau Excellence thiab Innovation nyob rau hauv Molecular Cell Sciences, lub koom haum ntawm Biochemistry thiab Cell Biology), Li Guohui Research Group ntawm Dalian lub koom haum ntawm Chemical Physics, Suav Academy ntawm Sciences, xibfwb Wang Xiongjun ntawm Guangzhou University thiab xibfwb Li Quanlin ntawm Zhongshan Tsev Kho Mob ntawm Fudan University koom ua ke luam tawm hauv Cell Tshawb Fawb phau ntawv xov xwm: Fructose-1, Thiab 6-bisphosphatase 1 dephosphorylates IκB thiab suppresses kab mob qog nqaij hlav hauv plab hauv cov ntawv tshawb fawb.
Txoj kev tshawb no tau qhia tias qhov tseem ceeb ntawm gluconeogenic metabolic enzyme, fructose 1, 6-diphosphatase 1 (FBP 1), tuaj yeem ua haujlwm raws li cov protein phosphatase, thiab txhais lub luag haujlwm tseem ceeb ntawm FBP 1-kev kho dephosphorylation ntawm I κ B. nyob rau hauv cov hnyuv carcinogenesis.
Nyob rau hauv txoj kev tshawb no, pab neeg tshawb fawb tau ua qhov kev ntsuam xyuas siab ntawm metabolic phosphatase los ntawm kev sim molecular docking thiab molecular dynamics (MD) simulations, thiab pom tias FBP 1, ib qho tseem ceeb metabolic enzyme nyob rau hauv txoj kev gluconeogenic, tuaj yeem siv los ua cov protein phosphatase. FBP 1 yog lub luag haujlwm rau catalyzing hydrolysis ntawm fructose 1, 6-diphosphate (F-1,6-BP) rau fructose 6-phosphate (F-6-P) .
Pab neeg tshawb fawb ntxiv tau txheeb xyuas I κ B raws li cov protein substrate rau FBP 1 dephosphorylation los ntawm phosphoproteomic tsom xam. Mechanistically, nyob rau hauv lub stimulation ntawm inflammatory yam xws li TNF , FBP 1 asparagine 213 (N213) ncaj qha interacts nrog I κ B thiab dephosphorylates serine 32 / 36 ntawm I κ B (S32 / 36), yog li inhibiting lub activation ntawm NF- κ B. teeb liab. MD simulations qhia tau hais tias lub catalytic mechanism ntawm FBP 1-mediated I κ B dephosphorylation zoo ib yam li F-1, 6-BP dephosphorylation, tshwj tsis yog tias kuv κ B dephosphorylation muaj zog dua barrier.
Ua haujlwm tau zoo, FBP 1- nyob ntawm qhov tsis ua haujlwm ntawm NF- κ B inhibits cov qog nqaij hlav hauv plab los ntawm kev ua kom cov qog hlwb ua rau mob stimuli thiab tiv thaiv kev mob ntawm cov pob txha pob txha-derived suppressor hlwb (MDSCs). Ntxiv mus, FBP 1 qhia nyob rau hauv cov qog nqaij hlav ntawm cov neeg mob qog nqaij hlav hauv plab tau cuam tshuam nrog NF- κ B ua kom muaj sia nyob, muaj sia nyob ntawm cov qog hlwb, thiab kev nkag mus ntawm MDSCs.
Qhov kev ua haujlwm no nthuav tawm cov enzyme metabolic FBP 1 los ua kom muaj kev ua haujlwm tshiab ntawm cov protein phosphatase, txheeb xyuas I κ B raws li cov protein substrate rau FBP 1 dephosphorylation, thiab tsim lub luag haujlwm tseem ceeb thiab cov txheej txheem ntawm FBP 1-kev kho dephosphorylation ntawm I κ B. nyob rau hauv cov qog nqaij hlav hauv plab.
Prof. Yang Weiwei ntawm Molecular Cell Excellence Center ntawm Suav Academy ntawm Sciences, Prof. Li Guohui ntawm Dalian Institute of Chemical Physics, xibfwb Wang Xiongjun Wang ntawm Guangzhou University, thiab Xib Fwb Li Quanlin los ntawm Tsev Kho Mob Zhongshan koom nrog Fudan University yog cov sib koom ua ke. cov neeg sau ntawv. Dr. Zhu Wencheng ntawm Center of Excellence for Molecular Cell, Dr. Chu Huiying, associate researcher of Dalian Institute of Chemical Physics, Prof. Zhang Yajuan ntawm Center of Excellence for Molecular Cells, Luo Tianhang, tus kws kho mob ntawm Shanghai Changhai Tsev Kho Mob, thiab Dr. Yu Hua ntawm Guangzhou University yog thawj tus kws sau ntawv ntawm daim ntawv no. Cov haujlwm tshawb fawb tau txhawb nqa los ntawm National Natural Science Foundation ntawm Tuam Tshoj, National Key Research thiab Development Program, thiab Youth Basic Research Program ntawm Suav Academy ntawm Sciences. Qhov kev tshawb fawb no tau txais kev txhawb nqa los ntawm Molecular Cell Center ntawm Excellence Cell Biology Technology platform, molecular biology technology platform, thiab tsiaj sim technology platform.
