title: Proteolysis targeting peptide (PROTAP) strategy for protein ubiquitination and degradation.
abstract: Ubiquitination proteasome pathway (UPP) is the most important and selective way to degrade proteins in vivo. Here, a novel proteolysis targeting peptide (PROTAP) strategy, composed of a target protein binding peptide, a linker and a ubiquitin E3 ligase recognition peptide, was designed to recruit both target protein and E3 ligase and then induce polyubiquitination and degradation of the target protein through UPP. In our study, the PROTAP strategy was proved to be a general method with high specificity using Bcl-xL protein as model target in vitro and in cells, which indicates that the strategy has great potential for in vivo application.
authors.affiliation: Department of Chemistry, Tsinghua University, Beijing 100084, China; The Ministry-Province Jointly Constructed Base for State Key Lab-Shenzhen Key Laboratory of Chemical Biology, The Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, Guangdong, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Chemistry, Tsinghua University, Beijing 100084, China; The Ministry-Province Jointly Constructed Base for State Key Lab-Shenzhen Key Laboratory of Chemical Biology, The Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, Guangdong, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Tan
authors.affiliation: Department of Chemistry, Tsinghua University, Beijing 100084, China; The Ministry-Province Jointly Constructed Base for State Key Lab-Shenzhen Key Laboratory of Chemical Biology, The Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, Guangdong, China.
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Xue
authors.affiliation: Shenzhen Kivita Innovative Drug Discovery Institute, Shenzhen 518055, Guangdong, China.
authors.forename: Jiakun
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Chemistry, Tsinghua University, Beijing 100084, China; The Ministry-Province Jointly Constructed Base for State Key Lab-Shenzhen Key Laboratory of Chemical Biology, The Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, Guangdong, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Chemistry, Tsinghua University, Beijing 100084, China; The Ministry-Province Jointly Constructed Base for State Key Lab-Shenzhen Key Laboratory of Chemical Biology, The Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, Guangdong, China. Electronic address: tan.ying@sz.tsinghua.edu.cn.
authors.forename: Ying
authors.initials: Y
authors.lastname: Tan
authors.affiliation: The Ministry-Province Jointly Constructed Base for State Key Lab-Shenzhen Key Laboratory of Chemical Biology, The Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, Guangdong, China; Department of Pharmacology and Pharmaceutical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Yuyang
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D001665:Binding Sites; D057809:HEK293 Cells; D006801:Humans; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D015202:Protein Engineering / Q000379:methods; D059748:Proteolysis; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D057149:Ubiquitinated Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination / Q000502:physiology*
chemical_list: D010455:Peptides; D057149:Ubiquitinated Proteins; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex
keywords: Bcl-xL; PROTAP; Proteasome; Proteolysis; Ubiquitination