Toll-interacting protein impacts on inflammation, autophagy, and vacuole trafficking in human disease

Li, Xiaoyun; Goobie, G.C.; Zhang, Yingze

doi:10.1007/s00109-020-01999-4

Cited by 23 publications

(21 citation statements)

References 75 publications

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“…These data are in contrast to our previous study using morpholino-mediated tollip knockdown in fish embryos [15] but are in agreement with similar observations on Tollip-deficient mice [21]. Consistent with the proposed role of Tollip in the regulation of innate immunity responses in mammals [16], we noted that its deficiency may affect basal expression levels of some inflammatory mediators and cytokines in zebrafish embryos. Furthermore, although embryos lacking Tollip tended to survive worse upon LPS challenge, inflammatory gene expression induced in response to LPS was not affected that is consistent with some data in mammalian models [23].…”

Section: Tollip-deficient Zebrafish Line Bears No Gross Phenotypic Al...supporting

confidence: 91%

“…Tollip deficiency does not aggravate swimming deficiency of the gba1 À/À mutant Having verified that Tollip has no apparent role in innate immune response to LPS during early development of fish and considering reported roles of Tollip in vacuolar and lysosomal trafficking (reviewed in ref. [16]), we wished to investigate whether Tollip contributes to a pathology involving disturbed lysosomal and protein homeostasis, such as Gaucher disease. So far, a protective role of Tollip against protein aggregation was shown in human cells in vitro [24] but not yet investigated in vivo in animal models.…”

Section: Tollip-deficient Zebrafish Line Bears No Gross Phenotypic Al...mentioning

confidence: 99%

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Tollip‐deficient zebrafish display no abnormalities in development, organ morphology or gene expression in response to lipopolysaccharide

et al. 2022

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Tollip is a multifunctional adaptor protein implicated in innate immunity, lysosomal trafficking/autophagy of protein aggregates and various signaling processes in mammalian models. To verify evolutionary conservation of these functions, we used CRISPR/Cas9 editing to construct a zebrafish line bearing a stable tollip knockout. In contrast to previously reported tollip morphants, Tollip-deficient fish display normal development until adulthood, are fertile, and have no apparent physiological defects. When challenged with lipopolysaccharide (LPS), inflammatory gene expression is unaffected. Moreover, Tollip deficiency does not aggravate swimming deficiency resulting from lysosomal dysfunction and proteotoxicity in a fish model of Gaucher disease. Thus, individual functions of Tollip may be organism-specific or manifest only upon certain conditions/challenges or disease backgrounds.

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Section: Tollip-deficient Zebrafish Line Bears No Gross Phenotypic Al...supporting

confidence: 91%

Section: Tollip-deficient Zebrafish Line Bears No Gross Phenotypic Al...mentioning

confidence: 99%

Tollip‐deficient zebrafish display no abnormalities in development, organ morphology or gene expression in response to lipopolysaccharide

et al. 2022

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“…Although the function of this "linker" region was previously unknown, it was recently shown to mediate the association of TOLLIP with STING (stimulator of interferon genes), stabilizing STING and maintaining cGAS-STING signaling in response to microbial pathogens 53 . Our work adds to the increasing evidence that TOLLIP is involved in a variety of signaling pathways 54,55 besides its original role in suppressing TLR and IL-1 receptor signaling during the resting state 56,57 . Whether the effect of TOLLIP on inflammatory signaling is distinct from its role in perinuclear targeting of RAS effector signaling complexes remains to be determined.…”

mentioning

confidence: 69%

CK2 signaling from TOLLIP-dependent perinuclear endosomes is an essential feature ofKRASandNRASmutant cancers

Basu

Luke

Karim

et al. 2022

Preprint

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Oncogenic RAS induces perinuclear translocation of the oncogenic kinases ERK1/2 and CK2 and the MAPK scaffold KSR1, forming endosomal signaling hubs termed perinuclear signaling centers (PSCs). PSCs are found in nearly all cancer cell lines and tumor tissues, suggesting that compartmentalization of oncogenic kinases drives tumorigenesis. We show here that the endosomal adaptor, TOLLIP, tethers RAB11A+ signaling endosomes containing CK2 and KSR1, but not ERK, to the perinuclear ER. TOLLIP binds to the KSR1 CA5 pseudo-kinase domain through a conserved region predicted to form a β-hairpin, thus anchoring PSCs to perinuclear endosomes. TOLLIP is perinuclear in cancer cells and KRasG12D-driven mouse tumors but is pan-cytoplasmic in non-transformed cells, correlating with the presence of PSCs. TOLLIP is required for proliferation/survival of KRAS mutant tumor cells but not HRAS, NRAS and BRAF cancers or non-transformed cells. KRasG12D-induced lung lesions in TollipKO/KO mice showed reduced numbers of carcinomatous lesions, implicating TOLLIP in progression to malignant cancer. Phosphoproteomics studies revealed that perinuclear CK2 phosphorylates specific substrates, particularly proteins involved in ribosome biogenesis and translation such as RIOK1 and eIF4B. In summary, our findings identify TOLLIP as a key signaling adaptor in KRAS tumors whose inhibition is a potential vulnerability of these cancers.

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“…With the development of the disease, both are prone to malignant transformation to form tumors. Some studies have found that excessive Toll-interacting protein expression may contribute to the deterioration of IPF, whereas decreased expression may be associated with the occurrence of IBD [25]. Interleukin-25 and CDKN2B-AS1 are associated with IPF and IBD [26,27].…”

Section: Discussionmentioning

confidence: 99%

Inflammatory bowel disease and risk of idiopathic pulmonary fibrosis: A protocol for systematic review and meta-analysis

et al. 2022

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Introduction Inflammatory bowel disease is a relapsing chronic gastrointestinal inflammatory disease. Idiopathic pulmonary fibrosis is a rare but serious extraintestinal pulmonary manifestation of inflammatory bowel disease. However, the relationship between these two conditions is unclear. Therefore, this study aims to elucidate this relationship through a systematic review and meta-analysis, focusing on the risk of idiopathic pulmonary fibrosis in patients with inflammatory bowel disease. Methods The systematic review will be outlined according to the Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols and its extension statement for reporting systematic reviews incorporating network meta-analyses of healthcare interventions: checklist and explanations. Original articles published in any language will be searched in the following databases: PubMed, Web of Science, EMBASE, Google Scholar, and Ovid. Observational studies that reveal an association measure between idiopathic pulmonary fibrosis and inflammatory bowel disease will be included (cross sectional, cohort, and case-control trials). Two independent reviewers will be assigned to evaluate study quality using the Newcastle–Ottawa scale for assessing the quality of non-randomized studies in meta-analyses. Sensitivity analyses will be conducted based on the quality of included studies. All relevant studies will be assessed based on the study type, sample size, inflammatory bowel disease subtype, odds ratio, confidence interval, treatment strategy, and follow-up. The Grading of Recommendations Assessment, Development, and Evaluation approach will be used to rate the quality of the evidence. Discussion The results of this meta-analysis may show that patients with inflammatory bowel disease are at higher risk of developing idiopathic pulmonary fibrosis. This study will be the first meta-analysis to focus on the association between inflammatory bowel disease and idiopathic pulmonary fibrosis. Exploring the relationship between the two conditions may further enhance our understanding of the pathogenesis of inflammatory bowel disease and idiopathic pulmonary fibrosis and promote the development of related research fields.

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Toll-interacting protein impacts on inflammation, autophagy, and vacuole trafficking in human disease

Cited by 23 publications

References 75 publications

Tollip‐deficient zebrafish display no abnormalities in development, organ morphology or gene expression in response to lipopolysaccharide

Tollip‐deficient zebrafish display no abnormalities in development, organ morphology or gene expression in response to lipopolysaccharide

CK2 signaling from TOLLIP-dependent perinuclear endosomes is an essential feature ofKRASandNRASmutant cancers

Inflammatory bowel disease and risk of idiopathic pulmonary fibrosis: A protocol for systematic review and meta-analysis

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