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NSD3S stabilizes MYC through hindering its interaction with FBXW7

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Journal of Molecular Cell Biology 2020年第6期12卷 438-447页

作者： Valentina Gonzalez-Pecchi Albert KKwan Sean Doyle Andrey AIvanov Yuhong Du Haian Fu Graduate Program in Cancer Biology Emory UniversityAtlantaGAUSA Department of Pharmacology and Chemical Biology Emory Chemical Biology Discovery CenterEmory UniversityAtlantaGAUSA Winship Cancer Institute Emory UniversityAtlantaGAUSA Department of Hematology&Medical Oncology Emory UniversityAtlantaGAUSA

The MYC transcription factor plays a key role in cell growth control. Enhanced MYC protein stability has been found to promote tumorigenesis. Thus, understanding how MYC stability is controlled may have significant implications for revealing MYC-driven growth regulatory mechanisms in physiological and pathological processes. Our previous work identified the histone lysine methyltransferase nuclear receptor binding SET domain protein 3 (NSD3) as a MYC modulator. NSD3S, a noncatalytic isoform of NSD3 with oncogenic activity, appears to bind, stabilize, and activate the transcriptional activity of MYC. However, the mechanism by which NSD3S stabilizes MYC remains to be elucidated. To uncover the nature of the interaction and the underlying mechanism of MYC regulation by NSD3S, we characterized the binding interface between both proteins by narrowing the interface to a 15-amino acid region in NSD3S that is partially required for MYC regulation. Mechanistically, NSD3S binds to MYC and reduces the association of F-box and WD repeat domain containing 7 (FBXW7) with MYC, which results in suppression of FBXW7-mediated proteasomal degradation of MYC and an increase in MYC protein half-life. These results support a critical role for NSD3S in the regulation of MYC function and provide a novel mechanism for NSD3S oncogenic function through inhibition of FBXW7-mediated degradation of MYC.

关键词： cancer FBXW7 MYC NSD3S protein–protein interaction

Global Landscape of Native protein Complexes in Synechocystis *** 6803

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Genomics, Proteomics & Bioinformatics 2022年第4期20卷 715-727页

作者： Chen Xu Bing Wang Lin Yang Lucas Zhongming Hu Lanxing Yi Yaxuan Wang Shenglan Chen Andrew Emili Cuihong Wan School of Life Sciences and Hubei Key Laboratory of Genetic Regulation and Integrative Biology Central China Normal UniversityWuhan 430079China Donnelly Centre for Cellular and Biomolecular Research University of TorontoTorontoON M5S 2E8Canada Departments of Biochemistry and Biology Boston UniversityBostonMA 02215USA

Synechocystis *** 6803(hereafter:Synechocystis)is a model organism for studying photosynthesis,energy metabolism,and environmental *** known as the first fully sequenced phototrophic organism,Synechocystis still has almost half of its proteome without functional *** this study,by using co-fractionation coupled with liquid chromatographytandem mass spectrometry(LC-MS/MS),we define 291 multi-protein complexes,encompassing24,092 protein±protein interactions(PPIs)among 2062 distinct gene *** information not only reveals the roles of photosynthesis in metabolism,cell motility,DNA repair,cell division,and other physiological processes,but also shows how protein functions vary from bacteria to higher plants due to changes in interaction *** also allows us to uncover the functions of hypothetical proteins,such as Sll0445,Sll0446,and Sll0447 involved in photosynthesis and cell motility,and Sll1334 involved in regulation of fatty acid *** we present the most extensive PPI data for Synechocystis so far,which provide critical insights into fundamental molecular mechanisms in cyanobacteria.

关键词： protein–protein interaction Cyanobacterium Co-fractionation Photosynthesis Function prediction

A Yeast BiFC-seq Method for Genome-wide Interactome Mapping

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Genomics, Proteomics & Bioinformatics 2022年第4期20卷 795-807页

作者： Limin Shang Yuehui Zhang Yuchen Liu Chaozhi Jin Yanzhi Yuan Chunyan Tian Ming Ni Xiaochen Bo Li Zhang Dong Li Fuchu He Jian Wang State Key Laboratory of Proteomics Beijing Proteome Research CenterNational Center for Protein Sciences(Beijing)Beijing Institute of LifeomicsBeijing 102206China Department of Biotechnology Beijing Institute of Radiation MedicineBeijing 100850China Department of Rehabilitation Medicine Nan LouKey Laboratory of Wound Repair and Regeneration of PLACollege of Life SciencesChinese PLA General HospitalBeijing 100853China School of Basic Medical Sciences Anhui Medical UniversityHefei 230032China

Genome-wide physical protein±protein interaction(PPI)mapping remains a major challenge for current ***,we reported a high-efficiency BiFC-seq method,yeastenhanced green fluorescent protein-based bimolecular fluorescence complementation(y EGFPBiFC)coupled with next-generation DNA sequencing,for interactome *** first applied y EGFP-BiFC method to systematically investigate an intraviral network of the Ebola ***-thirds(9/14)of known interactions of EBOV were recaptured,and five novel interactions were ***,we used the BiFC-seq method to map the interactome of the tumor protein *** identified 97 interactors of p53,more than three-quarters of which were ***,in a more complex background,we screened potential interactors by pooling two BiFC libraries together and revealed a network of 229 interactions among 205 *** results show that BiFC-seq is a highly sensitive,rapid,and economical method for genome-wide interactome mapping.

关键词： Bimolecular fluorescence complementation protein–protein interaction High-throughput Next-generation sequencing

Newfound Coding Potential of Transcripts Unveils Missing Members of Human protein Communities

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Genomics, Proteomics & Bioinformatics 2023年第3期21卷 515-534页

作者： Se´bastien Leblanc Marie *** Jean-Franc¸ois Jacques Amina M.Lekehal Andre´a Duclos Alexia Tremblay Alexis Bruggeman-Gascon Sondos Samandi Myle`ne Brunelle Alan A.Cohen Michelle S.Scott Xavier Roucou Department of Biochemistry and Functional Genomics Universite´de SherbrookeSherbrookeQC J1E 4K8Canada PROTEO Quebec Network for Research on Protein FunctionStructureand EngineeringQuebec CityQC G1V 0A6Canada Department of Family Medicine Universite´de SherbrookeSherbrookeQC J1H 5N4Canada

Recent proteogenomic approaches have led to the discovery that regions of the transcriptome previously annotated as non-coding regions[i.e.,untranslated regions(UTRs),open reading frames overlapping annotated coding sequences in a different reading frame,and non-coding RNAs]frequently encode proteins,termed alternative proteins(altProts).This suggests that previously identified protein–protein interaction(PPI)networks are partially incomplete because altProts are not present in conventional protein ***,we used the proteogenomic resource OpenProt and a combined spectrum-and peptide-centric analysis for the re-analysis of a highthroughput human network proteomics dataset,thereby revealing the presence of 261 altProts in the *** found 19 genes encoding both an annotated(reference)and an alternative protein interacting with each *** the 117 altProts encoded by pseudogenes,38 are direct interactors of reference proteins encoded by their respective parental ***,we experimentally validate several interactions involving *** data improve the blueprints of the human PPI network and suggest functional roles for hundreds of altProts.

关键词： Alternative protein protein network protein–protein interaction Pseudogene Affinity purification mass spectrometry

An Integrated Systems Biology Approach Identifies ZIKV and DENV Replication

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Genomics, Proteomics & Bioinformatics 2021年第1期19卷 108-122页

作者： Guang Song Emily M.Lee Jianbo Pan Miao Xu Hee-Sool Rho Yichen Cheng Nadia Whitt Shu Yang Jennifer Kouznetsova Carleen Klumpp-Thomas Samuel G.Michael Cedric Moore Ki-Jun Yoon Kimberly M.Christian Anton Simeonov Wenwei Huang Menghang Xia Ruili Huang Madhu Lal-Nag Hengli Tang Wei Zheng Jiang Qian Hongjun Song Guo-li Ming Heng Zhu Department of Pharmacology&Molecular Sciences Johns Hopkins School of MedicineBaltimoreMD 21205USA Department of Biological Science Florida State UniversityTallahasseeFL 32306USA Department of Ophthalmology Johns Hopkins School of MedicineBaltimoreMD 21205USA National Center for Advancing Translational Sciences National Institutes of HealthBethesdaMD 20892USA Sir Run Run Shaw Hospital Zhejiang University School of MedicineHangzhou 310016China Institute for Cell Engineering Johns Hopkins University School of MedicineBaltimoreMD 21205USA Department of Neuroscience and Mahoney Institute for Neurosciences Perelman School for MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA Department of Cell and Developmental Biology Perelman School for MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA Institute for Regenerative Medicine Perelman School for MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA The Epigenetics Institute Perelman School for MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA

The Zika virus(ZIKV)and dengue virus(DENV)flaviviruses exhibit similar replicative processes but have distinct clinical outcomes.A systematic understanding of virus–host protein–protein interaction networks can reveal cellular pathways critical to viral replication and disease *** we employed three independent systems biology approaches toward this ***,protein array analysis of direct interactions between individual ZIKV/DENV viral proteins and20,240 human proteins revealed multiple conserved cellular pathways and protein complexes,including proteasome ***,an RNAi screen of 10,415 druggable genes identified the host proteins required for ZIKV infection and uncovered that proteasome proteins were crucial in this ***,high-throughput screening of 6016 bioactive compounds for ZIKV inhibition yielded 134 effective compounds,including six proteasome inhibitors that suppress both ZIKV and DENV *** analyses of these orthogonal datasets pinpoint proteasomes as critical host machinery for ZIKV/DENV *** study provides multi-omics datasets for further studies of flavivirus–host interactions,disease pathogenesis,and new drug targets.

关键词： protein–protein interaction RNAi screening Chemical genetics screening Multi-omics

Computational Screening of Phase-separating proteins

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Genomics, Proteomics & Bioinformatics 2021年第1期19卷 13-24页

作者： Boyan Shen Zhaoming Chen Chunyu Yu Taoyu Chen Minglei Shi Tingting Li Department of Biomedical Informatics School of Basic Medical SciencesPeking University Health Science CenterBeijing 100191China Institute of Systems Biomedicine School of Basic Medical SciencesPeking University Health Science CenterBeijing 100191China MOE Key Laboratory of Bioinformatics Bioinformatics Division and Center for Synthetic&Systems BiologyBNRistSchool of MedicineTsinghua UniversityBeijing 100084China

Phase separation is an important mechanism that mediates the compartmentalization of proteins in *** that can undergo phase separation in cells share certain typical sequence features,like intrinsically disordered regions(IDRs)and multiple modular *** analysis tools are commonly used in the screening of these ***,current phase separation predictors are mostly designed for IDR-containing proteins,thus inevitably overlook the phase-separating proteins with relatively low IDR *** other than amino acid sequence could provide crucial information for identifying possible phase-separating proteins:protein–protein interaction(PPI)networks show multivalent interactions that underlie phase separation process;post-translational modifications(PTMs)are crucial in the regulation of phase separation behavior;spherical structures revealed in immunofluorescence(IF)images indicate condensed droplets formed by phase-separating proteins,distinguishing these proteins from non-phaseseparating ***,we summarize the sequence-based tools for predicting phaseseparating proteins and highlight the importance of incorporating PPIs,PTMs,and IF images into phase separation prediction in future studies.

关键词： Phase separation Prediction protein–protein interaction protein post-translational modification Immunofluorescence image

Dissecting the molecular basis of spike traits by integrating gene regulatory networks and genetic variation in wheat

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Plant Communications 2024年第5期5卷 57-74页

作者： Guo Ai Chao He Siteng Bi Ziru Zhou Ankui Liu Xin Hu Yanyan Liu Liujie Jin JiaCheng Zhou Heping Zhang Dengxiang Du Hao Chen Xin Gong Sulaiman Saeed Handong Su Caixia Lan Wei Chen Qiang Li Hailiang Mao Lin Li Hao Liu Dijun Chen Kerstin Kaufmann Khaled FAlazab Wenhao Yan National Key Laboratory of Crop Genetic Improvement Hubei Hongshan LaboratoryHuazhong Agricultural UniversityWuhan 430070China College of Plant Science and Technology Huazhong Agricultural UniversityWuhan 430070China Shenzhen Institute of Nutrition and Health Huazhong Agricultural UniversityWuhan 430070China Shenzhen Branch Guangdong Laboratory for Lingnan Modern AgricultureGenomeAnalysis Laboratory of the Ministry of AgricultureAgricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhen 518120China State Key Laboratory of Pharmaceutical Biotechnology School of Life SciencesNanjing UniversityNanjing 210023China Department for Plant Cell and Molecular Biology Institute for BiologyHumboldt-Universitat Zu Berlin10115 BerlinGermany Plant Research Department Nuclear Research CenterEgyptian Atomic Energy AuthorityCairo 13759Egypt

Spike architecture inﬂuences both grain weight and grain number per spike,which are the two major components of grain yield in bread wheat(Triticum aestivum L.).However,the complex wheat genome and the inﬂuence of various environmental factors pose challenges in mapping the causal genes that affect spike ***,we systematically identified genes involved in spike trait formation by integrating information on genomic variation and gene regulatory networks controlling young spike development in *** identified 170 loci that are responsible for variations in spike length,spikelet number per spike,and grain number per spike through genome-wide association study and meta-QTL *** constructed gene regulatory networks for young inﬂorescences at the double ridge stage and theﬂoret primordium stage,in which the spikelet meristem and theﬂoret meristem are predominant,respec-tively,by integrating transcriptome,histone modification,chromatin accessibility,eQTL,and protein–pro-tein interactome *** these networks,we identified 169 hub genes located in 76 of the 170 QTL regions whose polymorphisms are significantly associated with variation in spike *** functions of TaZF-B1,VRT-B2,and TaSPL15-A/D in establishment of wheat spike architecture were *** study provides valuable molecular resources for understanding spike traits and demonstrates that combining genetic analysis and developmental regulatory networks is a robust approach for dissection of complex traits.

关键词： bread wheat spike traits genetic variation protein–protein interaction gene regulatory network

Predicting overlapping protein complexes in weighted interactome networks

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Journal of Zhejiang University-Science C(Computers and Electronics) 2013年第10期14卷 756-765页

作者： Wen-yin NI Hui-jun XIONG Bi-hai ZHAO Sai HU Department of Information and Computing Science Changsha University

protein complexes play important roles in integrating individual gene products to perform useful cellular *** increasing mount of protein–protein interaction(PPI)data has enabled us to predict protein *** spite of the advances in these computational approaches and experimental techniques,it is impossible to construct an absolutely reliable PPI *** into account the reliability of interactions in the PPI network,we have constructed a weighted protein–protein interaction(WPPI)network,in which the reliability of each interaction is represented as a weight using the topology of the PPI *** overlaps are likely to have biological importance,we proposed a novel method named WN-PC(weighted network-based method for predicting protein complexes)to predict overlapping protein complexes on the WPPI *** proposed algorithm predicts neighborhood graphs with an aggregation coefficient over a threshold as candidate complexes,and binds attachment proteins to candidate ***,we have filtered redundant complexes which overlap other complexes to a very high extent in comparison to their density and size.A comprehensive comparison between competitive algorithms and our WN-PC method has been made in terms of the F-measure,coverage rate,and *** have applied WN-PC to two different yeast PPI data sets,one of which is a huge PPI network consisting of over 6000 proteins and 200000 *** results show that WN-PC outperforms the state-of-the-art *** think that our research may be helpful for other applications in PPI networks.

关键词： protein–protein interaction Weighted network Overlap

Oligomerization of drug transporters:Forms,functions,and mechanisms

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Acta Pharmaceutica Sinica B 2024年第5期14卷 1924-1938页

作者： Chunxu Ni Mei Hong College of Life Sciences South China Agricultural UniversityGuangzhou 510642China Guangdong Provincial Key Laboratory of protein Function and Regulation in Agricultural Organisms South China Agricultural UniversityGuangzhou 510642China

Drug transporters are essential players in the transmembrane transport of a wide variety of clinical *** broad substrate spectra and versatile distribution pattern of these membrane proteins infer their pharmacological and clinical *** our accumulating knowledge on the three-dimensional structure of drug transporters,their oligomerization status has become a topic of intense study due to the possible functional roles carried out by such kind of post-translational modification(PTM).In-depth studies of oligomeric complexes formed among drug transporters as well as their interactions with other regulatory proteins can help us better understand the regulatory mechanisms of these membrane proteins,provide clues for the development of novel drugs,and improve the therapeutic *** this review,we describe different oligomerization forms as well as their structural basis of major drug transporters in the ATP-binding cassette and solute carrier superfamilies,summarize our current knowledge on the influence of oligomerization for protein expression level and transport function of these membrane proteins,and discuss the regulatory mechanisms of ***,we highlight the challenges associated with the current oligomerization studies and propose some thoughts on the pharmaceutical application of this important drug transporter PTM.

关键词： Drug development Drug transporters Oligomerization protein expression protein–protein interaction Regulatory mechanism Structural basis Transport function