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Over the past 20 years, the integrative approach of the Gu Laboratory, combining biochemical analyses and advanced genetically manipulated mouse models has been instrumental to dissect the precise roles of protein modifications in regulating p53-mediated tumor suppression. The Gu lab has made significant contributions to establishing the roles of acetylation-mediated regulation of non-histone proteins. They established that site-specific acetylation plays a critical role in promoter-specific regulation of p53 targets. They discovered that the acidic domain containing proteins act as a new “reader” for acetylated substrates critically involved in acetylation-mediated actions. These studies have laid the foundation for the view that reversible acetylation is a general mechanism for regulation of non-histone proteins. Through in-depth investigation, the Gu lab has revealed that “dynamic ubiquitination” (polyubiquitination, monoubiquitination and deubiquitination) is the major mechanism by which the stability and subcellular localization of p53 protein are determined. They found that the deubiquitinase USP7 (also called HAUSP) interacts with both p53 and Mdm2; and is an important therapeutic target for human cancers through activating p53 and downregulating oncoproteins such as N-Myc. By using p53 acetylation-deficient mutant mice, the Gu lab has demonstrated that acetylation is required for p53-mediated cell-cycle arrest, senescence and apoptosis in vivo. Subsequently, they found that p53 is able to induce its tumor suppression through its metabolic targets including promoting ferroptosis.
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论文共 275 篇作者统计合作学者相似作者
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Weiwei Cui,Meng Guo,Dong Liu,Peng Xiao, Chuancheng Yang, Haidi Huang,Chunhui Liang, Yinghong Yang,Xiaolong Fu, Yudan Zhang, Jiaxing Liu,Shuang Shi,
Nature cell biologypp.1-14, (2024)
Wei Gu,Xiaofeng Huang,Pratik N P Singh, Sanlan Li,Ying Lan, Min Deng, Lauretta A Lacko,Jesus M Gomez-Salinero,Shahin Rafii, Michael P Verzi,Ramesh A Shivdasani,Qiao Zhou
Nature communicationsno. 1 (2024): 3595-3595
Xiaohui Lin,Dipika Gupta, Alina Vaitsiankova, Seema Khattri Bhandari, Kay Sze Karina Leung,Demis Menolfi,Brian J Lee,Helen R Russell, Steven Gershik,Wei Gu,Peter J McKinnon,Françoise Dantzer,
bioRxiv : the preprint server for biology (2024)
Nature Communicationsno. 1 (2024): 1-16
Genes & Diseasespp.101254, (2024)
Nature cancerno. 4 (2023): 564-581
Life sciences (2023): 121877-121877
Cell Death Discoveryno. 1 (2023): 1-1
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