The Tribbles(TRIB) family of pseudokinase proteins has been shown to play key roles in cell cycle, metabolic diseases, chronic inflammatory disease, and cancer development. A better understanding of the mechanisms of ...The Tribbles(TRIB) family of pseudokinase proteins has been shown to play key roles in cell cycle, metabolic diseases, chronic inflammatory disease, and cancer development. A better understanding of the mechanisms of TRIB pseudokinases could provide new insights for disease development and help promote TRIB proteins as novel therapeutic targets for drug discovery. At the 2 nd International Symposium on Tribbles and Diseases held on May 7–9, 2018 in Beijing, China, a group of leading Tribbles scientists reported their findings and ongoing studies about the effects of the different TRIB proteins in the areas of immunity, metabolism, fundamental cell biology and cancer. Here, we summarize important and insightful overviews from 4 keynote lectures, 13 plenary lectures and 8 short talks that took place during this meeting. These findings may offer new insights for the understanding of the roles of TRIB pseudokinases in the development of various diseases.展开更多
CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9-based genome editing has revolutionized func- tional genomics in many biological research fields. The specificity and potency of CR1SPR-Cas9 ge...CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9-based genome editing has revolutionized func- tional genomics in many biological research fields. The specificity and potency of CR1SPR-Cas9 genome editing make it ideal for investigating the function of genes in vivo (Hsu et al., 2014). Gene duplication is a key driver of evolu- tionary novelty (Taylor and Raes, 2004). However, duplicated genes with near-identical sequences and functional redun- dancy have posed challenges for genetic analysis (Woollard, 2005). The functions of duplicated genes can be assessed by simultaneous knockdown using homology-based methods such as RNA interference (RNAi) (Tischler et al., 2006), Generation of double or triple mutants is an alternative way to assess functional redundancy of duplicated genes, However, generation of such compound mutants by forward or reverse genetic methods is time consuming.展开更多
基金supported by National Key R&D Program of China(Grant No.2017YFA0205400,China)the National Natural Science Foundation of China(Grant Nos.81530093 and 81773781,China)+43 种基金Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(Grant No.2016-I2M-1-007,China)CAMS Central Public-interest Scientific Institution Basic Research Fund(Grant No.2017PT3104,China)supported by grants of the National Natural Science Foundation of China(Grant No.81874316,China)the CAMS Innovation Fund for Medical Sciences(Grant No.2016-I2M-3-008,China)supported by grants of from the BBSRC and NWCR(Grant Nos.1088 and 1097,UK)supported by grants of NSF(Grant No.IOS-1456023,USA)NIH(Grant No.NIH R21 CA197317,USA)supported by grants of Ministry of Education,Singapore(Grant Nos.MOE2014-T2-1-012 and 2012-T1-001-036,Singapore)supported by grants from the Health Research Council of New Zealandsupported by a Rutherford Discovery Fellowship from the New Zealand government administered by the Royal Society of New Zealandsupported by Funda??o para a Ciência e a Tecnologia(FCT)Research Center Grant UID/BIM/04773/2013 Centre for Biomedical Research 1334a research grant from Liga Portuguesa Contra o Cancro–Núcleo Regional do Sul(LPCC/NRS,Portugal)a FCT 2014 research grant SFRH/BPD/100434/2014a Pro Regem grant PD/BD/114258/2016(Portugal)supported by European Marie Sklodowska Curie ITN Project TRAIN-TRIBBLES Research and Innovation Network(Grant No.721532,EU)Innovation Network and the British Heart Foundation(PG/16/44/32146,UK)supported by grants from The Howat Foundation Ltd.(UK),Children with Cancer UK,Bloodwise and the Friends of Paul O'Gorman(UK)supported by grants of P-CREATE from Japan Agency for Medical Research and Developmentsupported by grants from the NIH(NIAID,USA),Alex's Lemonade Stand Foundation(USA)and the Samuel Waxman Cancer Research Foundation(USA)supported by European Marie Sklodowska Curie ITN Project TRAIN-TRIBBLES Research and Innovation Network(Grant No.721532,EU)the "Fondation Centaure"(RTRS),which supports a French transplantation research network,the IHU-Cesti project,the DHU Oncogreffefinancial support managed by the National Research Agency via the"Investment into the Future" program(Grant Nos.ANR-10-IBHU-005and ANR-11-LABX-0016-01,France)supported by Nantes Métropole and Région Pays de la Loire(France)supported by grants of the British Heart Foundation(PG/16/44/32146,UK)supported by European Marie Sklodowska Curie ITN Project TRAIN-TRIBBLES Research and Innovation Network(Grant No.721532,EU)supported by European Marie Sklodowska Curie ITN Project TRAIN-TRIBBLES Research and Innovation Network(Grant No.721532,EU)supported by a joint Ph.D studentship beween the A*Star Institute and the University of Sheffield(UK)supported by funding from the National Institutes of Health National Heart,Lung,and Blood Institute(R01HL141745,USA)supported by European Marie Sklodowska Curie ITN Project TRAIN-TRIBBLES Research and Innovation Network(Grant No.721532,EU)supported by European Marie Sklodowska Curie ITNProject TRAIN-TRIBBLES Research and Innovation Network(Grant No.721532,EU)supported by the National Natural Science Foundation of China(Grant No.81503128,China)CAMS Innovation Fund for Medical Sciences(Grant No.2016-I2M-1-008,China)supported by National Institute of Health(NS R01-035546,USA)supported by the National Natural Science Foundation of China(Grant No.81400140,China)CAMS Innovation Fund for Medical Sciences(Grant No.2016-I2M-1-011,China)supported by European Marie Sklodowska Curie ITN Project TRAIN-TRIBBLES Research and Innovation Network(Grant No.721532,EU)supported by Spanish Ministry of Economy and Competitiveness(MINECO)and Fondo Europeo de desarrollo Regional(FEDER)(Grant No.INNPACTO/IPT-2012-0614-010000,Spain)supported by the National Natural Science Foundation of China(Grant Nos.81400286 and 81530093,China)the CAMS Innovation Fund for Medical Sciences(Grant No.2016-I2M-1-010,China)supported by the National Natural Science Foundation of China(Grant Nos.81472717 and 81673474,China)Beijing Natural Science Foundation(Grant No.7162133,China)the CAMS Innovation Fund for Medical Sciences(Grant No.2016-I2M-1-007,China)supported by the National Natural Science Foundation of China(Grant No.81703564,China)supported by the National Natural Science Foundation of China(Grant No.81603129,China)
文摘The Tribbles(TRIB) family of pseudokinase proteins has been shown to play key roles in cell cycle, metabolic diseases, chronic inflammatory disease, and cancer development. A better understanding of the mechanisms of TRIB pseudokinases could provide new insights for disease development and help promote TRIB proteins as novel therapeutic targets for drug discovery. At the 2 nd International Symposium on Tribbles and Diseases held on May 7–9, 2018 in Beijing, China, a group of leading Tribbles scientists reported their findings and ongoing studies about the effects of the different TRIB proteins in the areas of immunity, metabolism, fundamental cell biology and cancer. Here, we summarize important and insightful overviews from 4 keynote lectures, 13 plenary lectures and 8 short talks that took place during this meeting. These findings may offer new insights for the understanding of the roles of TRIB pseudokinases in the development of various diseases.
基金supported by National Institutes of Health(NIH grant R01GM054657)to A.D.C
文摘CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9-based genome editing has revolutionized func- tional genomics in many biological research fields. The specificity and potency of CR1SPR-Cas9 genome editing make it ideal for investigating the function of genes in vivo (Hsu et al., 2014). Gene duplication is a key driver of evolu- tionary novelty (Taylor and Raes, 2004). However, duplicated genes with near-identical sequences and functional redun- dancy have posed challenges for genetic analysis (Woollard, 2005). The functions of duplicated genes can be assessed by simultaneous knockdown using homology-based methods such as RNA interference (RNAi) (Tischler et al., 2006), Generation of double or triple mutants is an alternative way to assess functional redundancy of duplicated genes, However, generation of such compound mutants by forward or reverse genetic methods is time consuming.