Crucial Roles of the RIP Homotypic Interaction Motifs of RIPK3 in RIPK1-Dependent Cell Death and Lymphoproliferative Disease

Crucial Roles of the RIP Homotypic Interaction Motifs of RIPK3 in RIPK1-Dependent Cell Death and Lymphoproliferative Disease

Summary: Receptor-interacting protein kinase 3 (RIPK3) has been identified as an essential regulator of necroptosis, apoptosis, and inflammatory signaling. RIPK3 contains an N-terminal kinase domain and a C-terminal RIP homotypic interaction motif (RHIM). However, the physiological roles of RIPK3 RH...

Full description

Bibliographic Details
Main Authors: Haiwei Zhang, Xiaoxia Wu, Xiaoming Li, Ming Li, Fang Li, Lingxia Wang, Xixi Zhang, Yue Zhang, Yan Luo, Hui Wang, Yiguo Jiang, Haibing Zhang
Format: Article
Language:English
Published: Elsevier 2020-05-01
Series:Cell Reports
Subjects:
RIPK3
RIPK1
necroptosis
Receptor-interacting protein homotypic interaction motifs
RHIM
lymphoproliferative disease
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124720306033
id doaj-b3b2b77b28b94f17bb6e84d1f0f67bbf
record_format Article
spelling doaj-b3b2b77b28b94f17bb6e84d1f0f67bbf2020-11-25T03:11:45ZengElsevierCell Reports2211-12472020-05-01317Crucial Roles of the RIP Homotypic Interaction Motifs of RIPK3 in RIPK1-Dependent Cell Death and Lymphoproliferative DiseaseHaiwei Zhang0Xiaoxia Wu1Xiaoming Li2Ming Li3Fang Li4Lingxia Wang5Xixi Zhang6Yue Zhang7Yan Luo8Hui Wang9Yiguo Jiang10Haibing Zhang11CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, ChinaCAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, ChinaCAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, ChinaCAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, ChinaCAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, ChinaCAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, ChinaCAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, ChinaDepartment of Anesthesiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Anesthesiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaSchool of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaInstitute for Chemical Carcinogenesis, State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, ChinaCAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China; Corresponding authorSummary: Receptor-interacting protein kinase 3 (RIPK3) has been identified as an essential regulator of necroptosis, apoptosis, and inflammatory signaling. RIPK3 contains an N-terminal kinase domain and a C-terminal RIP homotypic interaction motif (RHIM). However, the physiological roles of RIPK3 RHIM remain unclear. Here we generate knockin mice endogenously expressing the RIPK3 RHIM mutant, RIPK3V448P. Cells expressing RIPK3V448P are resistant to RIPK1 kinase-dependent apoptosis and necroptosis, and Ripk3V448P/V448P mice rescue embryonic lethality of Fadd-deficient mice by intercrossing. Strikingly, Ripk3V448P/V448PFadd−/− mice display more severe lymphoproliferative disease with a marked increase in abnormal CD3+B220+ lymphocytes compared with Ripk3−/−Fadd−/− mice. More importantly, these inflammatory morbidities in Ripk3V448P/V448PFadd−/− mice are profoundly inhibited by additional deletion of Ripk1. Taken together, these results reveal a previously unidentified physiological function of RHIM of RIPK3 in regulating RIPK1-dependent cell death and lymphoproliferative disease.http://www.sciencedirect.com/science/article/pii/S2211124720306033RIPK3RIPK1necroptosisReceptor-interacting protein homotypic interaction motifsRHIMlymphoproliferative disease
collection DOAJ
language English
format Article
sources DOAJ
author Haiwei Zhang
Xiaoxia Wu
Xiaoming Li
Ming Li
Fang Li
Lingxia Wang
Xixi Zhang
Yue Zhang
Yan Luo
Hui Wang
Yiguo Jiang
Haibing Zhang
spellingShingle Haiwei Zhang
Xiaoxia Wu
Xiaoming Li
Ming Li
Fang Li
Lingxia Wang
Xixi Zhang
Yue Zhang
Yan Luo
Hui Wang
Yiguo Jiang
Haibing Zhang
Crucial Roles of the RIP Homotypic Interaction Motifs of RIPK3 in RIPK1-Dependent Cell Death and Lymphoproliferative Disease
Cell Reports
RIPK3
RIPK1
necroptosis
Receptor-interacting protein homotypic interaction motifs
RHIM
lymphoproliferative disease
author_facet Haiwei Zhang
Xiaoxia Wu
Xiaoming Li
Ming Li
Fang Li
Lingxia Wang
Xixi Zhang
Yue Zhang
Yan Luo
Hui Wang
Yiguo Jiang
Haibing Zhang
author_sort Haiwei Zhang
title Crucial Roles of the RIP Homotypic Interaction Motifs of RIPK3 in RIPK1-Dependent Cell Death and Lymphoproliferative Disease
title_short Crucial Roles of the RIP Homotypic Interaction Motifs of RIPK3 in RIPK1-Dependent Cell Death and Lymphoproliferative Disease
title_full Crucial Roles of the RIP Homotypic Interaction Motifs of RIPK3 in RIPK1-Dependent Cell Death and Lymphoproliferative Disease
title_fullStr Crucial Roles of the RIP Homotypic Interaction Motifs of RIPK3 in RIPK1-Dependent Cell Death and Lymphoproliferative Disease
title_full_unstemmed Crucial Roles of the RIP Homotypic Interaction Motifs of RIPK3 in RIPK1-Dependent Cell Death and Lymphoproliferative Disease
title_sort crucial roles of the rip homotypic interaction motifs of ripk3 in ripk1-dependent cell death and lymphoproliferative disease
publisher Elsevier
series Cell Reports
issn 2211-1247
publishDate 2020-05-01
description Summary: Receptor-interacting protein kinase 3 (RIPK3) has been identified as an essential regulator of necroptosis, apoptosis, and inflammatory signaling. RIPK3 contains an N-terminal kinase domain and a C-terminal RIP homotypic interaction motif (RHIM). However, the physiological roles of RIPK3 RHIM remain unclear. Here we generate knockin mice endogenously expressing the RIPK3 RHIM mutant, RIPK3V448P. Cells expressing RIPK3V448P are resistant to RIPK1 kinase-dependent apoptosis and necroptosis, and Ripk3V448P/V448P mice rescue embryonic lethality of Fadd-deficient mice by intercrossing. Strikingly, Ripk3V448P/V448PFadd−/− mice display more severe lymphoproliferative disease with a marked increase in abnormal CD3+B220+ lymphocytes compared with Ripk3−/−Fadd−/− mice. More importantly, these inflammatory morbidities in Ripk3V448P/V448PFadd−/− mice are profoundly inhibited by additional deletion of Ripk1. Taken together, these results reveal a previously unidentified physiological function of RHIM of RIPK3 in regulating RIPK1-dependent cell death and lymphoproliferative disease.
topic RIPK3
RIPK1
necroptosis
Receptor-interacting protein homotypic interaction motifs
RHIM
lymphoproliferative disease
url http://www.sciencedirect.com/science/article/pii/S2211124720306033
work_keys_str_mv AT haiweizhang crucialrolesoftheriphomotypicinteractionmotifsofripk3inripk1dependentcelldeathandlymphoproliferativedisease
AT xiaoxiawu crucialrolesoftheriphomotypicinteractionmotifsofripk3inripk1dependentcelldeathandlymphoproliferativedisease
AT xiaomingli crucialrolesoftheriphomotypicinteractionmotifsofripk3inripk1dependentcelldeathandlymphoproliferativedisease
AT mingli crucialrolesoftheriphomotypicinteractionmotifsofripk3inripk1dependentcelldeathandlymphoproliferativedisease
AT fangli crucialrolesoftheriphomotypicinteractionmotifsofripk3inripk1dependentcelldeathandlymphoproliferativedisease
AT lingxiawang crucialrolesoftheriphomotypicinteractionmotifsofripk3inripk1dependentcelldeathandlymphoproliferativedisease
AT xixizhang crucialrolesoftheriphomotypicinteractionmotifsofripk3inripk1dependentcelldeathandlymphoproliferativedisease
AT yuezhang crucialrolesoftheriphomotypicinteractionmotifsofripk3inripk1dependentcelldeathandlymphoproliferativedisease
AT yanluo crucialrolesoftheriphomotypicinteractionmotifsofripk3inripk1dependentcelldeathandlymphoproliferativedisease
AT huiwang crucialrolesoftheriphomotypicinteractionmotifsofripk3inripk1dependentcelldeathandlymphoproliferativedisease
AT yiguojiang crucialrolesoftheriphomotypicinteractionmotifsofripk3inripk1dependentcelldeathandlymphoproliferativedisease
AT haibingzhang crucialrolesoftheriphomotypicinteractionmotifsofripk3inripk1dependentcelldeathandlymphoproliferativedisease
_version_ 1724653276809396224

Similar Items