Disordered methionine metabolism in MTAP/CDKN2A-deleted cancers leads to dependence on PRMT5

Autor: D. Randal Kipp, Craig Mickanin, Jeffery A. Porter, Albert Lai, Bing Zheng, Mark Stump, Yan Yan-Neale, John A. Tallarico, Young Shin Cho, Gregory R. Hoffman, Tobias Schmelzle, William R. Sellers, Samuel B. Ho, E. Robert McDonald, Kavitha Venkatesan, Yue Liu, Songping Zhao, Rosalie deBeaumont, Eric Billy, Ying Lin, Francesco Hofmann, Konstantinos J. Mavrakis, Vladimir Capka, Jianjun Yu, Antoine deWeck, Joshua T. McNamara, Emma Lees, Michael R. Schlabach, Hui Gao, Elizabeth R. Sprague, Nicholas Keen, Kristen Hurov, Kenneth Crawford, David A. Ruddy, David N. Ciccone, Guizhi Yang, Fallon Lin, Gregg McAllister, Justin Gu, Raymond Pagliarini, Alberto C. Vitari, Frank Stegmeier, Yingzi Yue, Hong Yin

Publikováno v: Science. 351:1208-1213

Tumors put in a vulnerable position Cancer cells often display alterations in metabolism that help fuel their growth. Such metabolic “rewiring” may also work against the cancer cells, however, by creating new vulnerabilities that can be exploited

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::f90e55c3fe4c3ecfba28cea037cdc9ce
https://doi.org/10.1126/science.aad5944

SPAK/OSR1 regulate NKCC1 and WNK activity: analysis of WNK isoform interactions and activation by T-loop trans-autophosphorylation

Autor: Dario R. Alessi, Jacob Thastrup, Maria Deak, Alberto C. Vitari, Fatema H. Rafiqi, Youcef Mehellou, Eulalia Pozo-Guisado

Publikováno v: Biochemical Journal

Mutations in the WNK [with no lysine (K) kinase] family instigate hypertension and pain perception disorders. Of the four WNK isoforms, much of the focus has been on WNK1, which is activated in response to osmotic stress by phosphorylation of its T-l

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3d214b7cc739690322d66483dbf9ed5c
https://doi.org/10.1042/bj20111879

Inflammasome-Dependent Release of the Alarmin HMGB1 in Endotoxemia

Autor: Amal O. Amer, Vishva M. Dixit, Anasuya Sarkar, Kevin J. Tracey, Lieselotte Vande Walle, Mark D. Wewers, Alberto C. Vitari, Thirumala-Devi Kanneganti, Mohamed Lamkanfi

Publikováno v: The Journal of Immunology. 185:4385-4392

Endotoxin administration recapitulates many of the host responses to sepsis. Inhibitors of the cysteine protease caspase 1 have long been sought as a therapeutic because mice lacking caspase 1 are resistant to LPS-induced endotoxic shock. According t

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::aacacf838a56e288ee61b53188af9362
https://doi.org/10.4049/jimmunol.1000803

The WNK1 and WNK4 protein kinases that are mutated in Gordon's hypertension syndrome phosphorylate and activate SPAK and OSR1 protein kinases

Autor: Maria Deak, Alberto C. Vitari, Dario R. Alessi, Nick A. Morrice

Publikováno v: Biochemical Journal. 391:17-24

Mutations in the human genes encoding WNK1 [with no K (lysine) protein kinase-1] and the related protein kinase WNK4 are the cause of Gordon's hypertension syndrome. Little is known about the molecular mechanism by which WNK isoforms regulate cellula

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::742e3fbf313a4d3ba15954fed9da89af
https://doi.org/10.1042/bj20051180

Project DRIVE: A Compendium of Cancer Dependencies and Synthetic Lethal Relationships Uncovered by Large-Scale, Deep RNAi Screening

Autor: Christine Stephan, William R. Sellers, Deborah Castelletti, Jeffery A. Porter, Julie L. Bernard, Sandra Mollé, Mark Stump, Tami Hood, Joshua M. Korn, Audrey Kauffmann, Giorgio G. Galli, Kristine Yu, Li Li, Marc Hattenberger, Javad Golji, Zainab Jagani, Marco Wallroth, Tobias Schmelzle, Philippe Megel, Raymond Pagliarini, Rosemary Barrett, Yingzi Yue, Richard S. Eldridge, Jan Weiler, Alberto C. Vitari, Konstantinos J. Mavrakis, Kalyani Gampa, Elizabeth Ackley, Rosalie deBeaumont, Qiong Shen, Joel Berger, Tanja Schouwey, Franklin Chung, E. Robert McDonald, Gregory McAllister, Christelle Stamm, Frances Shanahan, Aurore Desplat, Iris Kao, Thomas A. Perkins, Antoine de Weck, Kavitha Venkatesan, Albert Lai, Jennifer Johnson, Roland Widmer, David A. Ruddy, Avnish Kapoor, Brian Repko, François Gauter, Nicholas Keen, Tanushree Phadke, Eric Billy, Sosathya Sovath, Typhaine Martin, Elizabeth Frias, Justina X. Caushi, Vic E. Myer, Malini Varadarajan, William C. Forrester, Fei Feng, Hans Bitter, Ralph Tiedt, Yue Liu, Jing Zhang, Dorothee Abramowski, Dhiren Belur, Volker M. Stucke, Odile Weber, Mathias Jenal, Ali Farsidjani, Jianjun Yu, Rebecca Billig, JiaJia Feng, A. B. Meyer, Kristen Hurov, Veronica Gibaja, Michael D. Jones, Daisy Flemming, Donald A. Dwoske, Jilin Liu, Clara Delaunay, William Duong, Frank Buxton, Kaitlin J. Macchi, Saskia M. Brachmann, Alice T. Loo, Craig Mickanin, Francesco Hofmann, Frank Stegmeier, Kristy Haas, Gregory R. Hoffman, Marta Cortes-Cros, Roger Caothien, Shumei Liu, Serena J. Silver, Michael R. Schlabach, Emma Lees, Nadire Ramadan, Qiumei Liu, Zhenhai Gao

Publikováno v: Cell. 170:577-592.e10

Elucidation of the mutational landscape of human cancer has progressed rapidly and been accompanied by the development of therapeutics targeting mutant oncogenes. However, a comprehensive mapping of cancer dependencies has lagged behind and the disco

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::22974eb72276d42f1aa26407b00798f0
https://doi.org/10.1016/j.cell.2017.07.005