GSTDTAP

浏览/检索结果: 共10条,第1-10条 帮助

限定条件                
已选(0)清除 条数/页:   排序方式:
A dominant autoinflammatory disease caused by non-cleavable variants of RIPK1 期刊论文
NATURE, 2020, 577 (7788) : 109-+
作者:  Tao, Panfeng;  Sun, Jinqiao;  Wu, Zheming;  Wang, Shihao;  Wang, Jun;  Li, Wanjin;  Pan, Heling;  Bai, Renkui;  Zhang, Jiahui;  Wang, Ying;  Lee, Pui Y.;  Ying, Wenjing;  Zhou, Qinhua;  Hou, Jia;  Wang, Wenjie;  Sun, Bijun;  Yang, Mi;  Liu, Danru;  Fang, Ran;  Han, Huan;  Yang, Zhaohui;  Huang, Xin;  Li, Haibo;  Deuitch, Natalie;  Zhang, Yuan;  Dissanayake, Dilan;  Haude, Katrina;  McWalter, Kirsty;  Roadhouse, Chelsea;  MacKenzie, Jennifer J.;  Laxer, Ronald M.;  Aksentijevich, Ivona;  Yu, Xiaomin;  Wang, Xiaochuan;  Yuan, Junying;  Zhou, Qing
收藏  |  浏览/下载:23/0  |  提交时间:2020/07/03

Activation of RIPK1 controls TNF-mediated apoptosis, necroptosis and inflammatory pathways(1). Cleavage of human and mouse RIPK1 after residues D324 and D325, respectively, by caspase-8 separates the RIPK1 kinase domain from the intermediate and death domains. The D325A mutation in mouse RIPK1 leads to embryonic lethality during mouse development(2,3). However, the functional importance of blocking caspase-8-mediated cleavage of RIPK1 on RIPK1 activation in humans is unknown. Here we identify two families with variants in RIPK1 (D324V and D324H) that lead to distinct symptoms of recurrent fevers and lymphadenopathy in an autosomaldominant manner. Impaired cleavage of RIPK1 D324 variants by caspase-8 sensitized patients'  peripheral blood mononuclear cells to RIPK1 activation, apoptosis and necroptosis induced by TNF. The patients showed strong RIPK1-dependent activation of inflammatory signalling pathways and overproduction of inflammatory cytokines and chemokines compared with unaffected controls. Furthermore, we show that expression of the RIPK1 mutants D325V or D325H in mouse embryonic fibroblasts confers not only increased sensitivity to RIPK1 activation-mediated apoptosis and necroptosis, but also induction of pro-inflammatory cytokines such as IL-6 and TNF. By contrast, patient-derived fibroblasts showed reduced expression of RIPK1 and downregulated production of reactive oxygen species, resulting in resistance to necroptosis and ferroptosis. Together, these data suggest that human non-cleavable RIPK1 variants promote activation of RIPK1, and lead to an autoinflammatory disease characterized by hypersensitivity to apoptosis and necroptosis and increased inflammatory response in peripheral blood mononuclear cells, as well as a compensatory mechanism to protect against several pro-death stimuli in fibroblasts.


  
Molecular architecture of the human 17S U2 snRNP 期刊论文
NATURE, 2020, 583 (7815) : 310-+
作者:  Muench, David E.;  Olsson, Andre;  Ferchen, Kyle;  Pham, Giang;  Serafin, Rachel A.;  Chutipongtanate, Somchai;  Dwivedi, Pankaj;  Song, Baobao;  Hay, Stuart;  Chetal, Kashish;  Trump-Durbin, Lisa R.;  Mookerjee-Basu, Jayati;  Zhang, Kejian;  Yu, Jennifer C.
收藏  |  浏览/下载:18/0  |  提交时间:2020/07/03

The U2 small nuclear ribonucleoprotein (snRNP) has an essential role in the selection of the precursor mRNA branch-site adenosine, the nucleophile for the first step of splicing'  . Stable addition of U2 during early spliceosome formation requiresthe DEAD-box ATPase PRP5(2-7). Yeast U2 small nuclear RNA (snRNA) nucleotides that form base pairs with the branch site are initially sequestered in a branchpoint-interacting stem-loop (BSL)(8), but whether the human U2 snRNA folds in a similar manner is unknown. The U2 SF3B1 protein, a common mutational target in haematopoietic cancers(9), contains a HEAT domain (SF3B1(HEAT)) with an open conformation in isolated SF3b(10), but a closed conformation in spliceosomes(11), which is required for stable interaction between U2 and the branch site. Here we report a 3D cryo-electron microscopy structure ofthe human 17S U2 snRNP at a core resolution of 4.1 angstrom and combine it with protein crosslinking data to determine the molecular architecture of this snRNP. Our structure reveals that SF3B1(HEAT) interacts with PRP5 and TAT-SF1, and maintains its open conformation in U2 snRNP, and that U2 snRNA forms a BSL that is sandwiched between PRP5, TAT-SF1 and SF3B1(HEAT). Thus, substantial remodelling of the BSL and displacement of BSL-interacting proteins must occur to allow formation of the U2-branch-site helix. Our studies provide a structural explanation of why TAT-SF1 must be displaced before the stable addition of U2 to the spliceosome, and identify RNP rearrangements facilitated by PRP5 that are required for stable interaction between U2 and the branch site.


  
The dental proteome of Homo antecessor 期刊论文
NATURE, 2020, 580 (7802) : 235-+
作者:  Abram, Nerilie J.;  Wright, Nicky M.;  Ellis, Bethany;  Dixon, Bronwyn C.;  Wurtzel, Jennifer B.;  England, Matthew H.;  Ummenhofer, Caroline C.;  Philibosian, Belle;  Cahyarini, Sri Yudawati;  Yu, Tsai-Luen;  Shen, Chuan-Chou;  Cheng, Hai;  Edwards, R. Lawrence;  Heslop, David
收藏  |  浏览/下载:29/0  |  提交时间:2020/07/03

Analyses of the proteomes of dental enamel from Homo antecessor and Homo erectus demonstrate that the Early Pleistocene H. antecessor is a close sister lineage of later Homo sapiens, Neanderthal and Denisovan populations in Eurasia.


The phylogenetic relationships between hominins of the Early Pleistocene epoch in Eurasia, such as Homo antecessor, and hominins that appear later in the fossil record during the Middle Pleistocene epoch, such as Homo sapiens, are highly debated(1-5). For the oldest remains, the molecular study of these relationships is hindered by the degradation of ancient DNA. However, recent research has demonstrated that the analysis of ancient proteins can address this challenge(6-8). Here we present the dental enamel proteomes of H. antecessor from Atapuerca (Spain)(9,10) and Homo erectus from Dmanisi (Georgia)(1), two key fossil assemblages that have a central role in models of Pleistocene hominin morphology, dispersal and divergence. We provide evidence that H. antecessor is a close sister lineage to subsequent Middle and Late Pleistocene hominins, including modern humans, Neanderthals and Denisovans. This placement implies that the modern-like face of H. antecessor-that is, similar to that of modern humans-may have a considerably deep ancestry in the genus Homo, and that the cranial morphology of Neanderthals represents a derived form. By recovering AMELY-specific peptide sequences, we also conclude that the H. antecessor molar fragment from Atapuerca that we analysed belonged to a male individual. Finally, these H. antecessor and H. erectus fossils preserve evidence of enamel proteome phosphorylation and proteolytic digestion that occurred in vivo during tooth formation. Our results provide important insights into the evolutionary relationships between H. antecessor and other hominin groups, and pave the way for future studies using enamel proteomes to investigate hominin biology across the existence of the genus Homo.


  
Listeria monocytogenes impairs SUMOylation for efficient infection (vol 464, pg 1192, 2010) 期刊论文
NATURE, 2020, 580 (7805) : E20-E20
作者:  Abram, Nerilie J.;  Wright, Nicky M.;  Ellis, Bethany;  Dixon, Bronwyn C.;  Wurtzel, Jennifer B.;  England, Matthew H.;  Ummenhofer, Caroline C.;  Philibosian, Belle;  Cahyarini, Sri Yudawati;  Yu, Tsai-Luen;  Shen, Chuan-Chou;  Cheng, Hai;  Edwards, R. Lawrence;  Heslop, David
收藏  |  浏览/下载:8/0  |  提交时间:2020/07/03

An amendment to this paper has been published and can be accessed via a link at the top of the paper.


  
The evolutionary history of 2,658 cancers 期刊论文
NATURE, 2020, 578 (7793) : 122-+
作者:  Tao, Panfeng;  Sun, Jinqiao;  Wu, Zheming;  Wang, Shihao;  Wang, Jun;  Li, Wanjin;  Pan, Heling;  Bai, Renkui;  Zhang, Jiahui;  Wang, Ying;  Lee, Pui Y.;  Ying, Wenjing;  Zhou, Qinhua;  Hou, Jia;  Wang, Wenjie;  Sun, Bijun;  Yang, Mi;  Liu, Danru;  Fang, Ran;  Han, Huan;  Yang, Zhaohui;  Huang, Xin;  Li, Haibo;  Deuitch, Natalie;  Zhang, Yuan;  Dissanayake, Dilan;  Haude, Katrina;  McWalter, Kirsty;  Roadhouse, Chelsea;  MacKenzie, Jennifer J.;  Laxer, Ronald M.;  Aksentijevich, Ivona;  Yu, Xiaomin;  Wang, Xiaochuan;  Yuan, Junying;  Zhou, Qing
收藏  |  浏览/下载:33/0  |  提交时间:2020/07/03

Cancer develops through a process of somatic evolution(1,2). Sequencing data from a single biopsy represent a snapshot of this process that can reveal the timing of specific genomic aberrations and the changing influence of mutational processes(3). Here, by whole-genome sequencing analysis of 2,658 cancers as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)(4), we reconstruct the life history and evolution of mutational processes and driver mutation sequences of 38 types of cancer. Early oncogenesis is characterized by mutations in a constrained set of driver genes, and specific copy number gains, such as trisomy 7 in glioblastoma and isochromosome 17q in medulloblastoma. The mutational spectrum changes significantly throughout tumour evolution in 40% of samples. A nearly fourfold diversification of driver genes and increased genomic instability are features of later stages. Copy number alterations often occur in mitotic crises, and lead to simultaneous gains of chromosomal segments. Timing analyses suggest that driver mutations often precede diagnosis by many years, if not decades. Together, these results determine the evolutionary trajectories of cancer, and highlight opportunities for early cancer detection.


  
The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity (vol 483, pg 603, 2012) 期刊论文
NATURE, 2019, 565 (7738) : E5-E6
作者:  Barretina, Jordi;  Caponigro, Giordano;  Stransky, Nicolas;  Venkatesan, Kavitha;  Margolin, Adam A.;  Kim, Sungjoon;  Wilson, Christopher J.;  Lehar, Joseph;  Kryukov, Gregory V.;  Sonkin, Dmitriy;  Reddy, Anupama;  Liu, Manway;  Murray, Lauren;  Berger, Michael F.;  Monahan, John E.;  Morais, Paula;  Meltzer, Jodi;  Korejwa, Adam;  Jane-Valbuena, Judit;  Mapa, Felipa A.;  Thibault, Joseph;  Bric-Furlong, Eva;  Raman, Pichai;  Shipway, Aaron;  Engels, Ingo H.;  Cheng, Jill;  Yu, Guoying K.;  Yu, Jianjun;  Aspesi, Peter, Jr.;  de Silva, Melanie;  Jagtap, Kalpana;  Jones, Michael D.;  Wang, Li;  Hatton, Charles;  Palescandolo, Emanuele;  Gupta, Supriya;  Mahan, Scott;  Sougnez, Carrie;  Onofrio, Robert C.;  Liefeld, Ted;  MacConaill, Laura;  Winckler, Wendy;  Reich, Michael;  Li, Nanxin;  Mesirov, Jill P.;  Gabriel, Stacey B.;  Getz, Gad;  Ardlie, Kristin;  Chan, Vivien;  Myer, Vic E.;  Weber, Barbara L.;  Porter, Jeff;  Warmuth, Markus;  Finan, Peter;  Harris, Jennifer L.;  Meyerson, Matthew;  Golub, Todd R.;  Morrissey, Michael P.;  Sellers, William R.;  Schlegel, Robert;  Garraway, Levi A.
收藏  |  浏览/下载:22/0  |  提交时间:2019/11/27
Palaeoclimate constraints on the impact of 2 degrees C anthropogenic warming and beyond (vol 11, pg 474, 2018) 期刊论文
NATURE GEOSCIENCE, 2018, 11 (8) : 615-615
作者:  Fischer, Hubertus;  Meissner, Katrin J.;  Mix, Alan C.;  Abram, Nerilie J.;  Austermann, Jacqueline;  Brovkin, Victor;  Capron, Emilie;  Colombaroli, Daniele;  Daniau, Anne-Laure;  Dyez, Kelsey A.;  Felis, Thomas;  Finkelstein, Sarah A.;  Jaccard, Samuel L.;  McClymont, Erin L.;  Rovere, Alessio;  Sutter, Johannes;  Wolff, Eric W.;  Affolter, Stephane;  Bakker, Pepijn;  Ballesteros-Canovas, Juan Antonio;  Barbante, Carlo;  Caley, Thibaut;  Carlson, Anders E.;  Churakova (Sidorova), Olga;  Cortese, Giuseppe;  Cumming, Brian F.;  Davis, Basil A. S.;  de Vernal, Anne;  Emile-Geay, Julien;  Fritz, Sherilyn C.;  Gierz, Paul;  Gottschalk, Julia;  Holloway, Max D.;  Joos, Fortunat;  Kucera, Michal;  Loutre, Marie-France;  Lunt, Daniel J.;  Marcisz, Katarzyna;  Marlon, Jennifer R.;  Martinez, Philippe;  Masson-Delmotte, Valerie;  Nehrbass-Ahles, Christoph;  Otto-Bliesner, Bette L.;  Raible, Christoph C.;  Risebrobakken, Bjorg;  Goni, Maria F. Sanchez;  Arrigo, Jennifer Saleem;  Sarnthein, Michael;  Sjolte, Jesper;  Stocker, Thomas F.;  Alvarez, Patricio A. Velasquez;  Tinner, Willy;  Valdes, Paul J.;  Vogel, Hendrik;  Wanner, Heinz;  Yan, Qing;  Yu, Zicheng;  Ziegler, Martin;  Zhou, Liping
收藏  |  浏览/下载:12/0  |  提交时间:2019/04/09
Palaeoclimate constraints on the impact of 2 degrees C anthropogenic warming and beyond 期刊论文
NATURE GEOSCIENCE, 2018, 11 (7) : 474-485
作者:  Fischer, Hubertus;  Meissner, Katrin J.;  Mix, Alan C.;  Abram, Nerilie J.;  Austermann, Jacqueline;  Brovkin, Victor;  Capron, Emilie;  Colombaroli, Daniele;  Daniau, Anne-Laure;  Dyez, Kelsey A.;  Felis, Thomas;  Finkelstein, Sarah A.;  Jaccard, Samuel L.;  McClymont, Erin L.;  Rovere, Alessio;  Sutter, Johannes;  Wolff, Eric W.;  Affolter, Stephane;  Bakker, Pepijn;  Ballesteros-Canovas, Juan Antonio;  Barbante, Carlo;  Caley, Thibaut;  Carlson, Anders E.;  Churakova (Sidorova), Olga;  Cortese, Giuseppe;  Cumming, Brian F.;  Davis, Basil A. S.;  de Vernal, Anne;  Emile-Geay, Julien;  Fritz, Sherilyn C.;  Gierz, Paul;  Gottschalk, Julia;  Holloway, Max D.;  Joos, Fortunat;  Kucera, Michal;  Loutre, Marie-France;  Lunt, Daniel J.;  Marcisz, Katarzyna;  Marlon, Jennifer R.;  Martinez, Philippe;  Masson-Delmotte, Valerie;  Nehrbass-Ahles, Christoph;  Otto-Bliesner, Bette L.;  Raible, Christoph C.;  Risebrobakken, Bjorg;  Goni, Maria F. Sanchez;  Arrigo, Jennifer Saleem;  Sarnthein, Michael;  Sjolte, Jesper;  Stocker, Thomas F.;  Alvarez, Patricio A. Velasquez;  Tinner, Willy;  Valdes, Paul J.;  Vogel, Hendrik;  Wanner, Heinz;  Yan, Qing;  Yu, Zicheng;  Ziegler, Martin;  Zhou, Liping
收藏  |  浏览/下载:17/0  |  提交时间:2019/04/09
Glyoxal yield from isoprene oxidation and relation to formaldehyde: chemical mechanism, constraints from SENEX aircraft observations, and interpretation of OMI satellite data 期刊论文
ATMOSPHERIC CHEMISTRY AND PHYSICS, 2017, 17 (14)
作者:  Miller, Christopher Chan;  Jacob, Daniel J.;  Marais, Eloise A.;  Yu, Karen;  Travis, Katherine R.;  Kim, Patrick S.;  Fisher, Jenny A.;  Zhu, Lei;  Wolfe, Glenn M.;  Hanisco, Thomas F.;  Keutsch, Frank N.;  Kaiser, Jennifer;  Min, Kyung-Eun;  Brown, Steven S.;  Washenfelder, Rebecca A.;  Abad, Gonzalo Gonzalez;  Chance, Kelly
收藏  |  浏览/下载:12/0  |  提交时间:2019/04/09
Formation of alpha-chiral centers by asymmetric beta-C(sp(3))-H arylation, alkenylation, and alkynylation 期刊论文
SCIENCE, 2017, 355 (6324) : 499-+
作者:  Wu, Qing-Feng;  Shen, Peng-Xiang;  He, Jian;  Wang, Xiao-Bing;  Zhang, Forrest;  Shao, Qian;  Zhu, Ru-Yi;  Mapelli, Claudio;  Qiao, Jennifer X.;  Poss, Michael A.;  Yu, Jin-Quan
收藏  |  浏览/下载:7/0  |  提交时间:2019/11/27