Ask about this productRelated genes to: RIPK1 antibody
- Gene:
- RIPK1 NIH gene
- Name:
- receptor interacting serine/threonine kinase 1
- Previous symbol:
- -
- Synonyms:
- RIP
- Chromosome:
- 6p25.2
- Locus Type:
- gene with protein product
- Date approved:
- 1999-05-07
- Date modifiied:
- 2015-11-17
Related products to: RIPK1 antibody
Related articles to: RIPK1 antibody
- Regulated cell death is essential for tissue homeostasis, immune defense, and disease progression, yet the lipid-based regulatory mechanisms that coordinate cell death signaling remain incompletely understood. Protein palmitoylation is a dynamic and reversible lipid post-translational modification that controls protein membrane association, trafficking, stability, and signaling complex assembly. This review summarizes the regulatory roles of palmitoylation and depalmitoylation in major forms of regulated cell death, including apoptosis, necroptosis, pyroptosis, ferroptosis, and autophagy-related cell death. Particular attention is given to representative palmitoylated substrates, including Fas cell surface death receptor (Fas), receptor-interacting protein kinase 1 (RIPK1), NLR family pyrin domain containing 3 (NLRP3), gasdermin D (GSDMD), glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), autophagy-related 16 like 1 (ATG16L1), and Beclin1. These substrates illustrate how palmitoylation links membrane organization, metabolic status, inflammatory signaling, and cell fate decisions. Disease-oriented evidence further indicates that dysregulated palmitoylation contributes to cancer, neurodegenerative diseases, and inflammatory or immune-related disorders by modulating cell death resistance, inflammatory amplification, immune evasion, or impaired proteostasis. Current challenges include limited quantitative information on palmitoylation dynamics, incomplete evidence for some enzyme-substrate relationships, and insufficient distinction between disease-driving and secondary palmitoylation events. Targeting zinc finger Asp-His-His-Cys (zDHHC) palmitoyl acyltransferases, depalmitoylating enzymes, or specific palmitoylated substrates may provide new therapeutic opportunities. Overall, this review positions protein palmitoylation as a dynamic molecular switch linking lipid metabolism, membrane signaling, regulated cell death, and disease remodeling. - Source: PubMed
Publication date: 2026/06/11
Liu XiaozheCheng LikunLiu MingchengZhou MingzhuJiao BingzeLiu XuehanHu JianheLi YanweiXia Xiaojing - Autologous cellular immunotherapies, which rely on cytotoxic T lymphocytes (CTLs), are increasingly applied in different B-cell malignancies. The general assumption is that CTLs exert their cytolytic function through granzymes that induce apoptosis in the target cell. However, the killing mechanism of immunotherapeutic CTLs is not clearly elucidated. Using T-cell redirecting bispecific antibodies (BsAbs) and chimeric antigen receptor (CAR) T-cells we assessed which cell death pathways were activated in B cell line models as well as in primary material from CLL patients. We demonstrate that for cytotoxic T-cell killing of malignant B-cells by any of the treatment strategies, caspase activity was not essential. We could also exclude a role for TNF or TRAIL-mediated pathways. Using electron microscopy, CAR T-cell and BsAb-mediated cell death showed a mixed apoptotic/necroptotic phenotype. This was corroborated by knockout and chemical inhibition of the essential necroptosis proteins RIPK1, RIPK3, and MLKL. Necroptotic death of target cells correlated with the release of HMGB1 in the supernatant as well as various immunomodulatory molecules from the T-cells. Besides known immune activators IFN-y, IL-17 and IL-6, also anti-inflammatory IL-10 and IL1-RA were released. Moreover, the quantity of these immunomodulators was differentially affected after application of apoptosis versus necroptosis inhibitors. Together, these data demonstrate that (CAR) T-cell-mediated killing of lymphoma cells has a necroptotic arm which is correlated with modulation of the wider immune response. They imply that manipulation of the apoptotic versus necroptotic balance in immunotherapy could affect engagement of the autologous immune response. - Source: PubMed
Publication date: 2026/06/25
Both DemiSaura-Esteller JoséMartens AnneRietveld JoanneDerks IngridMes MorrisDuitman Jan WillemGrootemaat Anitavan der Wel NicoleKater ArnonHaselager MarcoEldering Eric - Necroptosis is closely associated with a variety of inflammatory diseases, with receptor-interacting serine/threonine-protein kinase 1 (RIPK1) serving as a key regulator of this signaling pathway. RIPK1 inhibitors based on the 5-benzyl-N-(5-methyl-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-yl)-1H-1,2,4-triazole-3-carboxamide scaffold have demonstrated potent anti-inflammatory activity, and two representatives, GSK2982772 and GSK3145095, advanced into Phase II clinical trials. However, their clinical development encountered significant challenges, highlighting the need for structurally novel RIPK1 inhibitors with improved pharmacological properties. Herein, GSK2982772 was selected as the starting point for rational optimization. Systematic structural modifications, including removal of the methylene linker in the benzyl moiety and replacement of the five-membered nitrogen-containing heterocycle with a phenyl ring, led to the design and synthesis of a series of novel biphenyl-based RIPK1 inhibitors. Importantly, our results demonstrate that the methylene linker is dispensable for anti-necroptosis activity and is not an essential pharmacophoric element in this scaffold. Among the synthesized compounds, W-1 exhibited approximately threefold stronger binding affinity toward RIPK1 than GSK2982772 (Kd = 21 nM vs. 60 nM). In addition to potent inhibition of necroptosis in vitro, W-1 significantly attenuated inflammatory responses in a mouse systemic inflammatory response syndrome (SIRS) model. Furthermore, W-1 displayed lower cytotoxicity and reduced predicted interactions with more than 70 toxicity-associated targets, suggesting a potentially improved safety profile. Although its pharmacokinetic properties remain to be further optimized, W-1 represents a promising starting point for the development of next-generation RIPK1 inhibitors. - Source: PubMed
Publication date: 2026/06/23
Wu YanranWu MengruWei JialeTao GuojingJia YongkangYang HuanHuang QingShi Ying - OTUD7B (Cezanne), a deubiquitinase of the Ovarian Tumor (OTU) domain family, regulates the ubiquitin-proteasome system and plays a role in maintaining cellular homeostasis. Its dysfunction is linked to the pathogenesis of multiple human diseases. In neoplastic diseases, OTUD7B is overexpressed in several solid tumors, including non-small cell lung cancer (NSCLC), gastric cancer, breast cancer, and pancreatic cancer. It promotes tumor cell proliferation, invasion, metastasis, and chemoresistance by stabilizing oncoproteins such as YAP1, ERα, and β-catenin/LEF1. This stabilization activates signaling pathways including NF-κB, Wnt/β-catenin, and Notch. However, its function is context-dependent. In diffuse large B-cell lymphoma (DLBCL), OTUD7B stabilizes TRAF3 to inhibit the non-canonical NF-κB pathway. In hepatocellular carcinoma (HCC), it deubiquitinates and stabilizes p53 to induce apoptosis. In both contexts, high expression correlates with favorable prognosis. In non-neoplastic diseases, OTUD7B also plays a dual role. In experimental autoimmune encephalomyelitis (EAE) models, it protects neurons by deubiquitinating RIPK1 and stabilizing GFAP. This action suppresses inflammation and promotes glial scar formation. Conversely, in pathological cardiac hypertrophy, its role is model-dependent. It protects against ferroptosis by stabilizing HNF4α in pressure-overload models. Under neurohormonal stimulation, it promotes hypertrophy by deubiquitinating SERCA2a and disrupting calcium homeostasis. These findings indicate that OTUD7B is a context-specific regulator. Its expression levels are associated with prognosis in multiple diseases. It shows potential as a diagnostic and prognostic biomarker and as a therapeutic target for specific conditions. This review systematically summarizes the molecular characteristics, expression regulation, physiological functions, and mechanisms of OTUD7B in neoplastic and non-neoplastic diseases. It also discusses the prospects and challenges of its clinical translation. - Source: PubMed
Publication date: 2026/06/09
Wang QingsongXu ShuqiongWen LihuiMeng JuanWang XianminLuo TongyongLuo RenjiuLi ZhujunLin DanYin Jun - Preeclampsia (PE) is a severe gestational disorder associated with impaired placental function. Necroptosis contributes substantially to trophoblast injury in PE, though the upstream epigenetic regulatory pathways are not yet fully elucidated. This study investigated how the deubiquitinase USP22 suppresses trophoblast necroptosis via epigenetic modulation of the KAT2A-SFRP1 axis. - Source: PubMed
Publication date: 2026/06/24
He LidanZhan FengZheng ShanLin Na