Regulation of RIPK1 activation by TAK1-mediated phosphorylation dictates apoptosis and necroptosis.
Jiefei Geng,Yasushi Ito,Linyu Shi,Palak Amin,Jiachen Chu,Amanda Tomie Ouchida,Adnan K. Mookhtiar,Heng Zhao,Daichao Xu,Bing Shan,Ayaz Najafov,Guangping Gao,Shizuo Akira,Junying Yuan,Junying Yuan +14 more
Reads0
Chats0
TLDR
In this article, the authors show that TAK-induced phosphorylation of RIPK1 in the intermediate domain by TAK1 plays a key role in regulating this critical decision.Abstract:
Stimulation of TNFR1 by TNFα can promote three distinct alternative mechanisms of cell death: necroptosis, RIPK1-independent and -dependent apoptosis. How cells decide which way to die is unclear. Here, we report that TNFα-induced phosphorylation of RIPK1 in the intermediate domain by TAK1 plays a key role in regulating this critical decision. Using phospho-Ser321 as a marker, we show that the transient phosphorylation of RIPK1 intermediate domain induced by TNFα leads to RIPK1-independent apoptosis when NF-κB activation is inhibited by cycloheximide. On the other hand, blocking Ser321 phosphorylation promotes RIPK1 activation and its interaction with FADD to mediate RIPK1-dependent apoptosis (RDA). Finally, sustained phosphorylation of RIPK1 intermediate domain at multiple sites by TAK1 promotes its interaction with RIPK3 and necroptosis. Thus, absent, transient and sustained levels of TAK1-mediated RIPK1 phosphorylation may represent distinct states in TNF-RSC to dictate the activation of three alternative cell death mechanisms, RDA, RIPK1-independent apoptosis and necroptosis.read more
Citations
More filters
Journal ArticleDOI
Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.
Lorenzo Galluzzi,Lorenzo Galluzzi,Ilio Vitale,Stuart A. Aaronson,John M. Abrams,Dieter Adam,Patrizia Agostinis,Emad S. Alnemri,Lucia Altucci,Ivano Amelio,David W. Andrews,David W. Andrews,Margherita Annicchiarico-Petruzzelli,Alexey V. Antonov,Eli Arama,Eric H. Baehrecke,Nickolai A. Barlev,Nicolas G. Bazan,Francesca Bernassola,Mathieu J.M. Bertrand,Katiuscia Bianchi,Mikhail V. Blagosklonny,Klas Blomgren,Christoph Borner,Patricia Boya,Catherine Brenner,Catherine Brenner,Michelangelo Campanella,Eleonora Candi,Didac Carmona-Gutierrez,Francesco Cecconi,Francis Ka-Ming Chan,Navdeep S. Chandel,Emily H. Cheng,Jerry E. Chipuk,John A. Cidlowski,Aaron Ciechanover,Gerald M. Cohen,Marcus Conrad,Juan R. Cubillos-Ruiz,Peter E. Czabotar,Peter E. Czabotar,Vincenzo D'Angiolella,Ted M. Dawson,Valina L. Dawson,Vincenzo De Laurenzi,Ruggero De Maria,Klaus-Michael Debatin,Ralph J. DeBerardinis,Mohanish Deshmukh,Nicola Di Daniele,Francesco Di Virgilio,Vishva M. Dixit,Scott J. Dixon,Colin S. Duckett,Brian David Dynlacht,Wafik S. El-Deiry,John W. Elrod,Gian Maria Fimia,Simone Fulda,Simone Fulda,Ana J. García-Sáez,Abhishek D. Garg,Carmen Garrido,Carmen Garrido,Evripidis Gavathiotis,Pierre Golstein,Eyal Gottlieb,Eyal Gottlieb,Douglas R. Green,Lloyd A. Greene,Hinrich Gronemeyer,Atan Gross,György Hajnóczky,J. Marie Hardwick,Isaac S. Harris,Michael O. Hengartner,Claudio Hetz,Hidenori Ichijo,Marja Jäättelä,Bertrand Joseph,Philipp J. Jost,Philippe Juin,William J. Kaiser,Michael Karin,Thomas Kaufmann,Oliver Kepp,Adi Kimchi,Richard N. Kitsis,Daniel J. Klionsky,Richard A. Knight,Sharad Kumar,Sam W. Lee,John J. Lemasters,Beth Levine,Andreas Linkermann,Stuart A. Lipton,Richard A. Lockshin,Richard A. Lockshin,Carlos López-Otín,Scott W. Lowe,Scott W. Lowe,Tom Luedde,Enrico Lugli,Marion MacFarlane,Frank Madeo,Michal Malewicz,Walter Malorni,Gwenola Manic,Jean-Christophe Marine,Seamus J. Martin,Jean-Claude Martinou,Jan Paul Medema,Patrick Mehlen,Pascal Meier,Sonia Melino,Edward A. Miao,Jeffery D. Molkentin,Ute M. Moll,Cristina Muñoz-Pinedo,Shigekazu Nagata,Gabriel Núñez,Andrew Oberst,Moshe Oren,Michael Overholtzer,Michele Pagano,Theocharis Panaretakis,Theocharis Panaretakis,Manolis Pasparakis,Josef M. Penninger,David M. Pereira,Shazib Pervaiz,Marcus E. Peter,Mauro Piacentini,Paolo Pinton,Jochen H. M. Prehn,Hamsa Puthalakath,Gabriel A. Rabinovich,Markus Rehm,Rosario Rizzuto,Cecília M. P. Rodrigues,David C. Rubinsztein,Thomas Rudel,Kevin M. Ryan,Emre Sayan,Luca Scorrano,Feng Shao,Yufang Shi,Yufang Shi,John Silke,John Silke,Hans-Uwe Simon,Antonella Sistigu,Brent R. Stockwell,Andreas Strasser,Gyorgy Szabadkai,Gyorgy Szabadkai,Gyorgy Szabadkai,Stephen W.G. Tait,Daolin Tang,Daolin Tang,Nektarios Tavernarakis,Andrew Thorburn,Yoshihide Tsujimoto,Boris Turk,Tom Vanden Berghe,Peter Vandenabeele,Matthew G. Vander Heiden,Matthew G. Vander Heiden,Andreas Villunger,Herbert W. Virgin,Karen H. Vousden,Domagoj Vucic,Erwin F. Wagner,Henning Walczak,David Wallach,Ying Wang,James A. Wells,Will Wood,Junying Yuan,Zahra Zakeri,Boris Zhivotovsky,Boris Zhivotovsky,Laurence Zitvogel,Gerry Melino,Gerry Melino,Guido Kroemer +186 more
TL;DR: The Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives.
Journal ArticleDOI
The molecular machinery of regulated cell death
TL;DR: The in-depth comprehension of each of these lethal subroutines and their intercellular consequences may uncover novel therapeutic targets for the avoidance of pathogenic cell loss.
Journal ArticleDOI
Caspase-8 induces cleavage of gasdermin D to elicit pyroptosis during Yersinia infection.
Joseph Sarhan,Beiyun C. Liu,Hayley I. Muendlein,Peng Li,Rachael Nilson,Amy Y. Tang,Anthony Rongvaux,Stephen C. Bunnell,Feng Shao,Douglas R. Green,Alexander Poltorak +10 more
TL;DR: The results uncover a form of caspase-8–mediated pyroptosis and suggest a hypothesis for the increased sensitivity of humans to Yersinia infection compared with the rodent reservoir.
Journal ArticleDOI
Necroptosis and RIPK1-mediated neuroinflammation in CNS diseases.
TL;DR: The evidence implicating necroptosis in neurological diseases is outlined and it is suggested that targeting RIPK1 might help to inhibit multiple cell death pathways and ameliorate neuroinflammation.
Journal ArticleDOI
Fundamental Mechanisms of Regulated Cell Death and Implications for Heart Disease
TL;DR: The most important conclusion relevant to heart disease is that regulated forms of cardiomyocyte death play important roles in both myocardial infarction with reperfusion (ischemia/reperfusion) and heart failure.
References
More filters
Journal ArticleDOI
Shared principles in NF-kappaB signaling
Matthew S. Hayden,Sankar Ghosh +1 more
TL;DR: The authors synthesize some of the basic principles that have emerged from studies of NF-kappaB, and aim to generate a more unified view of the regulation of the transcription factor.
Journal ArticleDOI
Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury
Alexei Degterev,Zhihong Huang,Michael Boyce,Yaqiao Li,Prakash Jagtap,Noboru Mizushima,Gregory D. Cuny,Timothy J. Mitchison,Michael A. Moskowitz,Junying Yuan +9 more
TL;DR: It is demonstrated that necroptosis contributes to delayed mouse ischemic brain injury in vivo through a mechanism distinct from that of apoptosis and offers a new therapeutic target for stroke with an extended window for neuroprotection.
Journal ArticleDOI
TAK1 is a ubiquitin-dependent kinase of MKK and IKK
TL;DR: The purification and identification of TRIKA2, which is composed of TAK1, TAB1 and TAB2, a protein kinase complex previously implicated in IKK activation through an unknown mechanism, indicate that ubiquitination has an important regulatory role in stress response pathways, including those of IKK and JNK.
Journal ArticleDOI
Identification of RIP1 kinase as a specific cellular target of necrostatins.
Alexei Degterev,Junichi Hitomi,Megan Germscheid,Irene L. Ch’en,Olga Korkina,Xin Teng,Derek W. Abbott,Derek W. Abbott,Gregory D. Cuny,Chengye Yuan,Gerhard Wagner,Stephen M. Hedrick,Scott A. Gerber,Alexey Lugovskoy,Alexey Lugovskoy,Junying Yuan +15 more
TL;DR: Necroptosis is a cellular mechanism of necrotic cell death induced by apoptotic stimuli in the form of death domain receptor engagement by their respective ligands under conditions where apoptotic execution is prevented and necrostatins are established as the first-in-class inhibitors of RIP1 kinase, the key upstream kinase involved in the activation of necroptosis.
Journal ArticleDOI
De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-κB signalling
Ingrid E. Wertz,Karen O'Rourke,Honglin Zhou,Michael Eby,L. Aravind,Somasekar Seshagiri,Ping Wu,Christian Wiesmann,Rohan T. Baker,David L. Boone,Averil Ma,Eugene V. Koonin,Vishva M. Dixit +12 more
TL;DR: A novel ubiquitin ligase domain is defined and two sequential mechanisms by which A20 downregulates NF-κB signalling are identified, both of which participate in mediating a distinct regulatory effect.