A missense mutation in the MLKL brace region promotes lethal neonatal inflammation and hematopoietic dysfunction

Autor: Cody C. Allison, Benjamin T. Kile, Esme C. Hatchell, Maria Kozlovskaia, Catriona McLean, Pradnya Gangatirkar, Gabriela Brumatti, Marc Pellegrini, Pamela A. McCombe, Julie Sheridan, Donald Metcalf, Klaus Warnatz, Natasha Silke, Maria C. Tanzer, Janelle E. Collinge, Seth L. Masters, Victoria E. Jackson, Jason Corbin, David B. Ascher, Dina Stockwell, Nicole Vlahovich, Zhixiu Li, James M. Murphy, Carola G. Vinuesa, Maria Kauppi, Ronald M. Laxer, John Reveille, Adrienne A. Hilton, John Silke, Ian J. Majewski, David Hughes, Gillian M. Tannahill, Melanie Bahlo, Christine Biben, Michael A. Silk, Maria A. Fiatarone Singh, Cathrine Hall, Peter E. Czabotar, Jian-Guo Zhang, Polly J. Ferguson, Sukhdeep K Spall, Carolyn A. de Graaf, Michael D. Stutz, Nils Venhoff, Alexander G. Bassuk, Zikou Liu, Holly Anderton, Michael S. Hildebrand, Tracy A. Willson, James A Rickard, Hiroyasu Nakano, Vicki Athanasopoulos, Matthew A. Brown, Samuel N. Young, Jens Thiel, Emma J. Petrie, Diep Chau, Sarah E Garnish, Sanae Miyake, Anne Tripaydonis, Warren S. Alexander, Allison Cox, Stefan Blum, Joanne M Hildebrand, Thomas S. Scerri, Kristin A Rigbye, Leila N. Varghese, Benjamin W. Darbro, Emma C. Josefsson, Ladina Di Rago

Publikováno v: Nature Communications, Vol 11, Iss 1, Pp 1-16 (2020)
Nature Communications
NATURE COMMUNICATIONS

MLKL is the essential effector of necroptosis, a form of programmed lytic cell death. We have isolated a mouse strain with a single missense mutation, MlklD139V, that alters the two-helix ‘brace’ that connects the killer four-helix bundle and reg

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ead403f9f5ff09d2fd122f72a19f707f
http://link.springer.com/article/10.1038/s41467-020-16819-z

The role of the thrombopoietin receptor MPL in myeloproliferative neoplasms: recent findings and potential therapeutic applications

Autor: Stefan N. Constantinescu, Isabelle Plo, Leila N. Varghese, William Vainchenker, Caroline Marty

Publikováno v: Expert review of hematology, Vol. 12, no. 6, p. 437-448 (2019)

INTRODUCTION: Classical Myeloproliferative Neoplasms (MPNs) include three disorders: Polycythemia Vera (PV), Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF). MPNs are associated with constitutive activation of JAK2 leading to persisten

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d94d29543063b574947995837688ed8f
https://doi.org/10.1080/17474086.2019.1617129

CALR mutant protein rescues the response of MPL p.R464G variant associated with CAMT to eltrombopag

Autor: Hana Raslova, Isabelle Plo, Paola Ballerini, Rémi Favier, Caroline Marty, Leila N. Varghese, Myriam Oufadem, Gabriel Levy, Nathalie Balayn, Francesca Basso-Valentina, Charlotte Boussard, William Vainchenker, Bénédicte Neven, Stefan N. Constantinescu

Publikováno v: Blood, Vol. 138, no. 6, p. 480-485 (2021)

Congenital amegakaryocytic thrombocytopenia (CAMT) is a severe inherited thrombocytopenia due to loss-of-function mutations affecting the thrombopoietin (TPO) receptor, MPL. Here, we report a new homozygous MPL variant responsible for CAMT in 1 consa

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3113b487ce67fdc5adb5accbe705d87c
https://hdl.handle.net/2078.1/251833

MPL mutations in essential thrombocythemia uncover a common path of activation with eltrombopag dependent on W491

Autor: Jean-Marc Zini, Serge Carillo, Benjamin Papoular, Stefan N. Constantinescu, Emilie Leroy, Bruno Cassinat, Ilyas Chachoua, Leila N. Varghese, Steven O. Smith, Gabriel Levy, Jean-Philippe Defour

Publikováno v: Blood
Blood, American Society of Hematology, 2020, 135 (12), pp.948-953. ⟨10.1182/blood.2019003240⟩
Blood, Vol. 135, no. 12, p. 948-953 (2020)

Mutations in the MPL gene encoding the human thrombopoietin receptor (TpoR) drive sporadic and familial essential thrombocythemias (ETs). We identified 2 ET patients harboring double mutations in cis in MPL, namely, L498W-H499C and H499Y-S505N. Using

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6f7a7f8fb43fc4232ec72a207873c81a
https://hal.umontpellier.fr/hal-03351305

Necroptosis signalling is tuned by phosphorylation of MLKL residues outside the pseudokinase domain activation loop

Autor: Samuel N. Young, Warren S. Alexander, John Silke, Maria C. Tanzer, Cathrine Hall, Andrew I. Webb, Leila N. Varghese, Anne Tripaydonis, Joanne M Hildebrand, James M. Murphy

Publikováno v: Biochemical Journal. 471:255-265

The pseudokinase MLKL (mixed lineage kinase domain-like), has recently emerged as a critical component of the necroptosis cell death pathway. Although it is clear that phosphorylation of the activation loop in the MLKL pseudokinase domain by the upst

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::37385b381f87e4aa38cbaf73f6a3e330
https://doi.org/10.1042/bj20150678