Clinical phenotype of a Chinese patient with RIPK1 deficiency due to novel mutation

Lin, Liang-In; Wang, Ying; Liu, Luyao; Ying, Wenjing; Wang, Wenjie; Sun, Bijun; Sun, Jinqiao; Wang, Xiaochuan

doi:10.1016/j.gendis.2019.10.008

Cited by 19 publications

(23 citation statements)

References 22 publications

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“…Given that these are life-long immunological disorders, dysregulation in the adaptive immune system can ensue. From 2018 till now, six independent groups have reported patients with RIPK1-associated immunodeficiency or autoinflammatory diseases (9)(10)(11)(12)(13)(14). Patients with RIPK1 deficiency and RIPK1 non-cleavable mutations present with distinct clinical manifestations.…”

Section: Ripk1-related Human Immune Diseasesmentioning

confidence: 99%

“…Unlike postnatal lethality of Ripk1 constitutive knockout mice, patients with RIPK1 biallelic LoF mutations were born alive, however, they suffered from severe and potentially lethal immunodeficiency ( 9 – 12 ), and one of them had autoinflammatory manifestations ( 12 ). The associated phenotypes include recurrent viral, bacterial, and/or fungal infections, early-onset inflammatory bowel disease (IBD), and progressive polyarthritis.…”

Section: Ripk1-related Human Immune Diseasesmentioning

confidence: 99%

“…In recent years, multiple studies in model organisms have provided better understandings of the intricate biological functions of RIPK1. However, the role of RIPK1 in the regulation of immune responses has not been fully understood until very recently with the identification of RIPK1deficiency Immunodeficiency 57 With Autoinflammation; OMIM: # 618108 (9)(10)(11)(12) and the autoinflammatory disease named CRIA (Cleavage-resistant RIPK1-Induced Autoinflammatory) (13,14). Both disorders are characterized by a profound dysregulation of cytokine expression and cell death pathways, and severe immune dysfunction.…”

Section: Introductionmentioning

confidence: 99%

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RIPK1-Associated Inborn Errors of Innate Immunity

et al. 2021

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RIPK1 (receptor-interacting serine/threonine-protein kinase 1) is a key molecule for mediating apoptosis, necroptosis, and inflammatory pathways downstream of death receptors (DRs) and pattern recognition receptors (PRRs). RIPK1 functions are regulated by multiple post-translational modifications (PTMs), including ubiquitination, phosphorylation, and the caspase-8-mediated cleavage. Dysregulation of these modifications leads to an immune deficiency or a hyperinflammatory disease in humans. Over the last decades, numerous studies on the RIPK1 function in model organisms have provided insights into the molecular mechanisms of RIPK1 role in the maintenance of immune homeostasis. However, the physiological role of RIPK1 in the regulation of cell survival and cell death signaling in humans remained elusive. Recently, RIPK1 loss-of-function (LoF) mutations and cleavage-deficient mutations have been identified in humans. This review discusses the molecular pathogenesis of RIPK1-deficiency and cleavage-resistant RIPK1 induced autoinflammatory (CRIA) disorders and summarizes the clinical manifestations of respective diseases to help with the identification of new patients.

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Section: Ripk1-related Human Immune Diseasesmentioning

confidence: 99%

Section: Ripk1-related Human Immune Diseasesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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RIPK1-Associated Inborn Errors of Innate Immunity

et al. 2021

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“…Serine/threonine or tyrosine residues are important sites in the KD of RIPK1 since these are acceptors of phosphate groups, hence amino acid substitutions can affect RIPK1 functions [ 58 ]. An important conserved residue in the catalytic domain of RIPK1 is serine 25 (S25), which is phosphorylated by the IKKα/β in TNFR1 complex I, repressing the kinase activity of RIPK1 with consequent inhibition of apoptosis/necroptosis [ 49 ]. Interestingly, phospho-mimetic S25D mutation in MEFs and in mice revealed protection against TNF stimulation in condition of IKK inhibition highlighting its protective role [ 49 ].…”

Section: Biological Relevance Of Ripk1mentioning

confidence: 99%

“…An important conserved residue in the catalytic domain of RIPK1 is serine 25 (S25), which is phosphorylated by the IKKα/β in TNFR1 complex I, repressing the kinase activity of RIPK1 with consequent inhibition of apoptosis/necroptosis [ 49 ]. Interestingly, phospho-mimetic S25D mutation in MEFs and in mice revealed protection against TNF stimulation in condition of IKK inhibition highlighting its protective role [ 49 ]. Serine 89 also is a novel regulatory residue on RIPK1 which might control programmed necrosis [ 60 ].…”

Section: Biological Relevance Of Ripk1mentioning

confidence: 99%

The Role of Necroptosis: Biological Relevance and Its Involvement in Cancer

Torre

Nebbioso

Stunnenberg

et al. 2021

Cancers

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Regulated cell death mechanisms are essential for the maintenance of cellular homeostasis. Evasion of cell death is one of the most important hallmarks of cancer. Necroptosis is a caspase independent form of regulated cell death, investigated as a novel therapeutic strategy to eradicate apoptosis resistant cancer cells. The process can be triggered by a variety of stimuli and is controlled by the activation of RIP kinases family as well as MLKL. The well-studied executor, RIPK1, is able to modulate key cellular events through the interaction with several proteins, acting as strategic crossroads of several molecular pathways. Little evidence is reported about its involvement in tumorigenesis. In this review, we summarize current studies on the biological relevance of necroptosis, its contradictory role in cancer and its function in cell fate control. Targeting necroptosis might be a novel therapeutic intervention strategy in anticancer therapies as a pharmacologically controllable event.

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Functions of the RIP kinase family members in the skin

Urwyler-Rösselet,

Tanghe,

Devos

et al. 2023

Cell. Mol. Life Sci.

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The receptor interacting protein kinases (RIPK) are a family of serine/threonine kinases that are involved in the integration of various stress signals. In response to several extracellular and/or intracellular stimuli, RIP kinases engage signaling cascades leading to the activation of NF-κB and mitogen-activated protein kinases, cell death, inflammation, differentiation and Wnt signaling and can have kinase-dependent and kinase-independent functions. Although it was previously suggested that seven RIPKs are part of the RIPK family, phylogenetic analysis indicates that there are only five genuine RIPKs. RIPK1 and RIPK3 are mainly involved in controlling and executing necroptosis in keratinocytes, while RIPK4 controls proliferation and differentiation of keratinocytes and thereby can act as a tumor suppressor in skin. Therefore, in this review we summarize and discuss the functions of RIPKs in skin homeostasis as well as the signaling pathways involved.

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Clinical phenotype of a Chinese patient with RIPK1 deficiency due to novel mutation

Cited by 19 publications

References 22 publications

RIPK1-Associated Inborn Errors of Innate Immunity

RIPK1-Associated Inborn Errors of Innate Immunity

The Role of Necroptosis: Biological Relevance and Its Involvement in Cancer

Functions of the RIP kinase family members in the skin

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