RIPK3 Proteine (RIPK3)

Human Receptor-Interacting serine-threonine Kinase 3 (RIPK3) Interaktionspartner

1. Data indicate that receptor-interacting protein 3 (RIP3) is down-regulated in multiple cancers.

2. The major function of RIP1 kinase activity in TNF-induced necroptosis is to autophosphorylate serine 161. This specific phosphorylation then enables RIP1 to recruit RIP3 and form a functional necrosome, a central controller of necroptosis.

3. RIPK3-dependent cell death and inflammasome activation in FLT3-internal-tandem-duplication-expressing leukemia-initiating cells

4. The necroptosis-inducing kinase RIPK3 reduces adipose tissue inflammation and glucose intolerance.

5. We showed that RIP3 spontaneously drives a necroptosis-induced inflammation in established intestinal cell lines and in ileal/colonic samples from IBD patients.

6. These data demonstrate that caspase-8 functions in synovial antigen-presenting cells to regulate the response to inflammatory stimuli by controlling RIPK3 action, and this delicate balance maintains homeostasis within the joint.

7. The induced expression of RIP3 by UHRF1 RNAi depends on the presence of Sp1. Remarkably, the ectopic expression of RIP3 in RIP3-null cancer cells results in a decrease in tumor growth in mice. Therefore, our findings offer insights into RIP3 expression control in cancer cells and suggest an inhibitory effect of RIP3 on tumorigenesis.

8. 2-hydroxyglutarate bound to DNMT1 and stimulated its association with the RIP3 promoter, inducing hypermethylation that reduces RIP3 protein and consequently impaired RIP3-dependent necroptosis.

9. the in vivo effects were diametrically reversed with RIP3 deletion or RIP1 blockade, resulting in marked tumor protection. The dichotomy between the in vivo and in vitro results suggests that the microenvironmental milieu resulting from RIP1/RIP3 signaling is likely responsible for its protumorigenic effects

10. Shikonin induces glioma cell necroptosis in vitro by reactive oxygen species overproduction and promoting RIP1/RIP3 necrosome formation.

11. In critically ill trauma patients, plasma levels of the necroptosis mediator RIP3 at 48 h were associated with AKI stage and RBC transfusions.

12. our results reveal that the necroptosis adaptor RIPK3 has key anti-inflammatory and anti-tumoral functions in the intestine, and define RIPK3 as a novel colon tumor suppressor

13. adhesion-induced eosinophil cytolysis takes place through RIPK3-MLKL-dependent necroptosis, which can be counterregulated by autophagy

14. Renal clear cell carcinoma cells cells express increased amounts of RIPK1 and RIPK3 and are poised to undergo necroptosis in response to TNFR1 signaling.

15. The results highlight a new role of TSC2 in protecting glioblastoma against photodynamic therapy-induced cell death, and TSC2 and YWHAZ as new RIP3 partners.

16. inactivation of RIP1/RIP3 resulted in reduction of SOCS1 protein levels and partial differentiation of AML cells. AML cells with inactivated RIP1/RIP3 signaling show increased sensitivity to IFN-gamma-induced differentiation.

17. results reveal a pathway for MLKL-dependent programmed necrosis that is executed in the absence of RIPK3 and potentially drives the pathogenesis of severe liver diseases.

18. Necroptosis signaling is modulated by the kinase RIPK1 and requires the kinase RIPK3 and the pseudokinase MLKL. (Review)

19. Data identify RIPK3 and the inflammasome as key tumor suppressors in acute myeloid leukemia (AML).

Mouse (Murine) Receptor-Interacting serine-threonine Kinase 3 (RIPK3) Interaktionspartner

1. Embryonic fibroblasts from RIP3 knockout mice are resistant to necrosis and RIP3 knockout animals are devoid of inflammation inflicted tissue damage in an acute pancreatitis model.

2. Using an RNA interference screen, the kinase RIP3 was identified as a crucial activator for programmed necrosis induced by TNF and during virus infection; RIP3 regulates necrosis-specific RIP1 phosphorylation.

3. By comparing the phosphorylation sites in wild-type and RIP3-knockdown L929 cells, 174, 167, and 177 distinct phosphorylation sites were revealed to be dependent on RIP3 at the 0.5, 2, and 4 h time points after TNF treatment, respectively.

4. The B-Raf(V600E) inhibitor dabrafenib selectively inhibits RIP3 and alleviates acetaminophen-induced liver injury.

5. RIP3-dependent necroptosis modulates post-ischaemic adverse remodelling in a mouse model of myocardial infarction

6. RIP3 deletion suppresses inflammation response.

7. Lymphocyte infiltrations in the adipocyte tissue and in skin lesions of ApoE single-knockout mice were significantly mitigated in ApoE/RIP3 double-knockout mice

8. Rip3 removal did not reduce pancreatic tissue damage, but rather enhanced this damage, though without an increase in local inflammation and even a reduction in macrophage counts.

9. Results suggest that RGC-5 cell necroptosis following oxygen glucose deprivation is mediated by a RIP3-induced increase in oxidative stress

10. RIP3-mediated necroptosis is a major mechanism of enhanced inflammation and lung tissue injury in high dose LPS- induced severe ARDS in mice

11. Our results suggest that RIP3 enhances innate immune responses against ocular MCMV infection via activation of the inflammasome and nuclear factor-kappaB, which also leads to inflammation and death of bystander cells by multiple pathways including apoptosis and necroptosis.

12. necroptosis contributes to ischemic brain injury induced by oxygen-glucose deprivation and middle cerebral artery occlusion and implicate HIF-1alpha, RIP1, RIP3, and MLKL in necroptosis.

13. miR-155 up-regulation in macrophages by Salmonella infection causes macrophage death and it may be mediated by both RIP1/3-related necroptosis and PARP-1-mediated necrosis.

14. key player in the degenerative process in dystrophin-deficient muscles

15. melatonin treatment inhibited the Ripk3-PGAM5-CypD-mPTP cascade and thus reduced cellular necroptosis, conferring a protective advantage to the endothelial system in IR stress.

16. Aldehyde dehydrogenase 2 deficiency negates chronic low-to-moderate alcohol consumption-induced cardioprotecion possibly via ROS-dependent apoptosis and RIP1/RIP3/MLKL-mediated necroptosis.

17. The major function of RIP1 kinase activity in TNF-induced necroptosis is to autophosphorylate serine 161. This specific phosphorylation then enables RIP1 to recruit RIP3 and form a functional necrosome, a central controller of necroptosis.

18. Deficiency in RIPK3 attenuated serum and lung cytokines, lung injury and neutrophil infiltration and lung and gut apoptosis. These data suggest that RIPK3, in part, is responsible for the systemic inflammatory response in neonatal sepsis.

19. Our results demonstrated that Ripk3 was strongly upregulated in murine hearts subjected to IR injury and cardiomyocytes treated with LPS and H2O2..the present study helps to elucidate how necroptosis is mediated by ER stress, via the calcium overload /XO/ROS/mPTP opening axis

20. RIP3-ablation attenuated oxidative stress, inflammation and apoptosis in astrocytes, which was dependent on AMPKalpha activation.