Article
Medicine, Research & Experimental
Yongsam Jo, Byeongmo Kim, Deug Y. Shin
Summary: The study revealed that the anti-apoptotic E3 ubiquitin ligase AREL1 ubiquitinates and promotes the degradation of Metaxin 2 (MTX2), which enhances TNF-induced necroptosis when expressed with Metaxin 1 (MTX1). However, AREL1 inhibits necroptosis even in cells expressing Metaxin proteins, indicating that inhibiting AREL1-dependent ubiquitination of MTX2 may sensitize tumor cells to TNF-induced necroptosis.
EXPERIMENTAL AND THERAPEUTIC MEDICINE
(2021)
Review
Cell Biology
Lin Liu, Najoua Lalaoui
Summary: RIPK1 is a key regulator of inflammation, post-translationally regulated by ubiquitylations, phosphorylations and caspase-8-mediated cleavage. Dysregulations of these modifications can cause inflammatory diseases, but may be advantageous for cancer treatment.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Maria Feoktistova, Roman Makarov, Amir S. Yazdi, Diana Panayotova-Dimitrova
Summary: TNF-induced cell death is regulated by RIPK1 and TRADD, with RIPK1 playing a critical role in apoptosis and necroptosis in the absence of IAPs, while TRADD functions as a negative regulator of NIK stabilization and ripoptosome formation. Additionally, MAPK signaling activation does not require RIPK1 and TRADD, and partial repression of NF-kappa B activation in these cells does not sensitize them to TNF due to the lack of NIK stabilization. RIPK1 is essential for preventing TRADD ubiquitination and degradation during TNF signaling, highlighting the intricate balance between cell death and survival.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Jin Hwa Cho, Kidae Kim, Sung Ah Kim, Sungryul Park, Bi-Oh Park, Jong-Hwan Kim, Seon-Young Kim, Min Jee Kwon, Myeong Hoon Han, Sung Bae Lee, Byoung Chul Park, Sung Goo Park, Jeong-Hoon Kim, Sunhong Kim
Summary: OTUD5 has been identified as a novel positive regulator of the mTOR complex signaling pathways, playing a role in stabilizing specific proteins to degrade the inhibitory protein DEPTOR of mTOR, affecting physiological phenotypes such as cell size and autophagy. Our results suggest a positive feedback loop between OTUD5 and the mTOR signaling pathway.
CELL DEATH AND DIFFERENTIATION
(2021)
Review
Cell Biology
Lei Yuan, Peiyao Li, Qian Zheng, Hui Wang, Hui Xiao
Summary: Ubiquitination and deubiquitination play important roles in apoptosis and apoptotic cell clearance, and are crucial for normal development and immune diseases.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Endocrinology & Metabolism
Tatiana Takiishi, Peng Xiao, Marie Franchimont, Eduardo H. Gilglioni, Erick N. Arroba, Esteban N. Gurzov, Mathieu J. M. Bertrand, Alessandra K. Cardozo
Summary: This study investigated the role of RIPK1 activation in immune-mediated diabetes or diet induced obesity (DIO). The results showed that Ripk1S25D/S25D mice had normal glucose metabolism and β-cell function. Furthermore, there were no significant differences in immune-mediated diabetes and DIO between Ripk1S25D/S25D and Ripk1+/+ mice.
MOLECULAR METABOLISM
(2023)
Review
Immunology
Wanjin Li, Junying Yuan
Summary: RIPK1 acts as a crucial regulator in TNFR1 signaling, controlling cell death, survival, and inflammation. The activation of RIPK1 kinase not only promotes necroptosis and apoptosis, but also induces the transcription of inflammatory cytokines, leading to inflammation. Moreover, activated RIPK1 translocates to the nucleus to interact with the BAF complex, facilitating chromatin remodeling and transcription. This review highlights the proinflammatory role of RIPK1 kinase in human neurodegenerative diseases and discusses the potential of targeting RIPK1 kinase for the treatment of inflammatory pathology in human diseases.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Fabian Schorn, J. Paul Werthenbach, Mattes Hoffmann, Mila Daoud, Johanna Stachelscheid, Lars M. Schiffmann, Ximena Hildebrandt, Su Ir Lyu, Nieves Peltzer, Alexander Quaas, Domagoj Vucic, John Silke, Manolis Pasparakis, Hamid Kashkar
Summary: This study established a mouse model with mutated cIAP1/2, revealing the regulation of TNF signaling by cIAPs and their independent functions from RIPK1 and RIPK3. The study provides important molecular insights into TNF signaling.
Editorial Material
Cell Biology
Weiwei Qi, Junying Yuan
Summary: Super-resolution microscopy reveals the architectural features of necrosomes formed by RIPK1-RIPK3 during necroptosis, shedding light on the signaling processes from RIPK1 to RIPK3 and from RIPK3 to RIPK1 when mediating necroptosis and apoptosis, respectively.
NATURE CELL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Orsolya Bilkei-Gorzo, Tiaan Heunis, Jose Luis Marin-Rubio, Francesca Romana Cianfanelli, Benjamin Bernard Armando Raymond, Joseph Inns, Daniela Fabrikova, Julien Peltier, Fiona Oakley, Ralf Schmid, Anetta Hartlova, Matthias Trost
Summary: This study reveals the importance of phagosomal ubiquitylation and the E3 ubiquitin ligase RNF115 in regulating innate immune functions during bacterial infections.
Article
Cell Biology
Xiaolian Cai, Ziwen Zhou, Junji Zhu, Xing Liu, Gang Ouyang, Jing Wang, Zhi Li, Xiong Li, Huangyuan Zha, Chunchun Zhu, Fangjing Rong, Jinghua Tang, Qian Liao, Xiaoyun Chen, Wuhan Xiao
Summary: OTUD3 plays opposite roles in response to RNA and DNA virus infection by removing distinct types of ubiquitination from RIG-I/MDA5 and cGAS, thereby regulating immune responses. OTUD3 can suppress RNA virus-triggered immunity and enhance DNA virus-triggered immunity.
Article
Chemistry, Medicinal
Adam G. Bond, Conner Craigon, Kwok-Ho Chan, Andrea Testa, Athanasios Karapetsas, Rotimi Fasimoye, Thomas Macartney, J. Julian Blow, Dario R. Alessi, Alessio Ciulli
Summary: This study describes the design and development of a new protein degradation system utilizing a variant of the Brd4 bromodomain as a degradation tag. The system effectively degrades BromoTagged proteins in a fast, selective manner, showing favorable pharmacokinetic profile in mice. This system expands the arsenal of chemical genetic degradation tools for manipulating protein levels and exploring therapeutic potential in cells and in vivo.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Cell Biology
Martin P. Schwalm, Lena M. Berger, Maximilian N. Meuter, James D. Vasta, Cesear R. Corona, Sandra Roehm, Benedict-Tilman Berger, Frederic Farges, Sebastian M. Beinert, Franziska Preuss, Viktoria Morasch, Vladimir V. Rogov, Sebastian Mathea, Krishna Saxena, Matthew B. Robers, Susanne Mueller, Stefan Knapp
Summary: E3 ligases play a crucial role in regulating protein homeostasis by recruiting substrate proteins to the proteasomal degradation machinery. Recent research has focused on the Baculovirus IAP Repeat (BIR) family of E3 ligases, which contain a structurally conserved but diverse protein interaction domain. The Inhibitors of Apoptosis (IAP) family, which typically have three BIR domains, are promising drug targets. However, there is currently a lack of assay tools to evaluate the selectivity of inhibitors in this target area.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Cell Biology
Zhijun Liu, Francis Ka-Ming Chan
Summary: RIP kinases, including RIPK1 and RIPK3, are key adaptors in inflammatory and cell death signaling pathways. Their activities are tightly regulated by post-translational modifications and environmental factors, which are crucial for proper immune responses and tissue homeostasis.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Isabelle Coornaert, Pauline Puylaert, Giullia Marcasolli, Mandy O. J. Grootaert, Peter Vandenabeele, Guido R. Y. De Meyer, Wim Martinet
Summary: Myeloid-specific RIPK1 gene deletion can reduce plaque formation and necrotic cell numbers, slowing down the progression of atherosclerosis. However, over time, the accumulation of free apoptotic and necrotic cells may result in an increase in plaque and necrotic core size.
Review
Radiology, Nuclear Medicine & Medical Imaging
Fei-Fei An, Mark Chan, Harikrishna Kommidi, Richard Ting
AMERICAN JOURNAL OF ROENTGENOLOGY
(2016)
Article
Endocrinology & Metabolism
Ye Wang, Fei-Fei An, Mark Chan, Beth Friedman, Erik A. Rodriguez, Roger Y. Tsien, Omer Aras, Richard Ting
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2017)
Article
Cell Biology
Xin Xu, Matko Kalac, Michael Markson, Mark Chan, Joshua D. Brody, Govind Bhagat, Rosalind L. Ang, Diana Legarda, Scott J. Justus, Feng Liu, Qingshan Li, Huabao Xiong, Adrian T. Ting
CELL DEATH & DISEASE
(2020)
Article
Biochemistry & Molecular Biology
Justin Taft, Michael Markson, Diana Legarda, Roosheel Patel, Mark Chan, Louise Malle, Ashley Richardson, Conor Gruber, Marta Martin-Fernandez, Grazia M. S. Mancini, Jan A. M. van Laar, Philomine van Pelt, Sofija Buta, Beatrijs H. A. Wokke, Ira K. D. Sabli, Vanessa Sancho-Shimizu, Pallavi Pimpale Chavan, Oskar Schnappauf, Raju Khubchandani, Muserref Kasap Cuceoglu, Seza Ozen, Daniel L. Kastner, Adrian T. Ting, Ivona Aksentijevich, Iris H. I. M. Hollink, Dusan Bogunovic
Summary: The loss of TBK1 leads to decreased IFN-I induction but affects autoinflammation and TNF-induced cell death, and treatment with anti-TNF can improve the clinical condition of patients.
Article
Multidisciplinary Sciences
Rosalind L. Ang, Mark Chan, Diana Legarda, John P. Sundberg, Shao-Cong Sun, Virginia L. Gillespie, Nicholas Chun, Peter S. Heeger, Huabao Xiong, Sergio A. Lira, Adrian T. Ting
Summary: The study found that the phenotype of Sharpin(cpdm/cpdm) mice is dependent on CYLD, which suppresses TNF- and RIPK1-dependent cell death. Regulation of CYLD can ameliorate inflammatory symptoms such as dermatitis in mice.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Medicine, Research & Experimental
Nicholas Chun, Rosalind L. Ang, Mark Chan, Robert L. Fairchild, William M. Baldwin, Julian K. Horwitz, Jesse D. Gelles, Jerry Edward Chipuk, Michelle A. Kelliher, Vasile Pavlov, Yansui Li, Dirk Homann, Peter S. Heeger, Adrian T. Ting
Summary: The research indicates that TNF released by T cells can activate RIPK1-dependent cell death program in target cells, leading to target cell lysis. This phenomenon not only accelerates murine cardiac allograft rejection but also synergizes with anti-PD1 administration to destroy checkpoint blockade-resistant murine melanoma.