Pellino 1 Is Required for Interleukin-1 (IL-1)-mediated Signaling through Its Interaction with the IL-1 Receptor-associated Kinase 4 (IRAK4)-IRAK-Tumor Necrosis Factor Receptor-associated Factor 6 (TRAF6) Complex

Jiang, Zhengfan; Johnson, H. Jan; Nie, Huiqing; Qin, Jinzhong; Bird, Timothy A.; Li, Xiaoxia

doi:10.1074/jbc.m212112200

Cited by 163 publications

(205 citation statements)

References 29 publications

(36 reference statements)

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“…Three mammalian homologues (Pellino1, 2 and 3) have since been identified, with Pellino3 being expressed in two spliced forms [35][36][37][38][39]. Given that Drosophila Pellino was discovered based on its interaction with Pelle, mammalian Pellino proteins have been characterized by their potential to interact with IRAK molecules.…”

Section: Irak Polyubiquitylation and Tlr/il-1r Signallingmentioning

confidence: 99%

“…Given that Drosophila Pellino was discovered based on its interaction with Pelle, mammalian Pellino proteins have been characterized by their potential to interact with IRAK molecules. Overexpression studies have shown that mammalian Pellino proteins interact with both IRAK1 and IRAK4 [36,37,[40][41][42][43]. Furthermore, a yeast two-hybrid screen using IRAK4 as bait independently identified Pellino2 as a protein-binding partner [40].…”

Section: Irak Polyubiquitylation and Tlr/il-1r Signallingmentioning

confidence: 99%

“…Furthermore, a yeast two-hybrid screen using IRAK4 as bait independently identified Pellino2 as a protein-binding partner [40]. Under physiological conditions, the Pellino-IRAK interactions are likely to be dependent on prior TLR or IL-1R stimulation because endogenous IRAK-Pellino associations are not observed in resting cells but manifest in response to stimulation by IL-1 [33,[35][36][37]44] and LPS [44].…”

Section: Irak Polyubiquitylation and Tlr/il-1r Signallingmentioning

confidence: 99%

See 2 more Smart Citations

The Pellino family: IRAK E3 ligases with emerging roles in innate immune signalling

Moynagh

2009

Trends in Immunology

132

102

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Section: Irak Polyubiquitylation and Tlr/il-1r Signallingmentioning

confidence: 99%

Section: Irak Polyubiquitylation and Tlr/il-1r Signallingmentioning

confidence: 99%

Section: Irak Polyubiquitylation and Tlr/il-1r Signallingmentioning

confidence: 99%

See 1 more Smart Citation

The Pellino family: IRAK E3 ligases with emerging roles in innate immune signalling

Moynagh

2009

Trends in Immunology

132

102

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“…4 demonstrate that TRIF is also required for the lipid-A-stimulated production of the intracellular proteins Pellino 1, RICK/Rip2, SOCS1, and SOCS3 that are considered to be involved in pattern recognition and cytokine receptor signaling. Whereas Pellino 1 appears to form an intermediate signaling complex with IRAK-1, IRAK-4, and TRAF6, leading to the activation of NF-‹ B [36], analysis of gene-deficient macrophages has shown that RICK/Rip2 is required for immune cell activation by Nod proteins and for optimal cytokine production in response to TLR2, TLR3, and TLR4 agonists [37,38]. SOCS1 and SOCS3 have been identified as critical negative regulators of IFN-+ and gp130 signaling, respectively [39].…”

Section: Trif Regulates the Expression Of Genes Encoding Immune Recepmentioning

confidence: 99%

Identification of a TLR4‐ and TRIF‐dependent activation program of dendritic cells

et al. 2004

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Dendritic cell activation by Toll-like receptors (TLR) is crucial for the generation of protective immune responses. In addition to the common myeloid differentiation factor 88 (MyD88)-dependent signaling pathway, TLR4 engages the adaptor protein Toll/IL-1 receptor (TIR)-domain-containing adaptor inducing IFN-g (TRIF), leading to interferon regulatory factor 3 (IRF-3) activation and type I interferon production. Using microarray expression profiling we now identify TRIF as a major regulator of the TLR4-triggered activation program of dendritic cells. We show that the expression of 47% of the genes that are responsive to TLR4 stimulation in wild-type dendritic cells is significantly altered in cells carrying a loss-of-function mutation of TRIF. Specifically, expression of IL-12, IL-18, and IL-23 was impaired in the absence of functional TRIF, suggesting that TLR4-promoted Th1 responses are TRIFdependent. Furthermore, we provide evidence that TRIF regulates TLR4-mediated gene expression both by type I IFN-dependent and -independent mechanisms. Whereas dendritic cell production of CXCL10 and CCL12 was dependent on both TRIF and the type I interferon receptor, expression of IL-6 required TRIF but not type I interferon activity. Functional TRIF was also required for the normal induction of numerous genes considered important for host defense against diverse pathogens. Together, these data therefore identify TRIF as a crucial regulator of TLR4-dependent dendritic cell responses.

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“…Peli1 interacts with interleukin‐1 receptor‐associated kinase‐4, interleukin‐1 receptor‐associated kinase, and tumor necrosis factor receptor–associated factor‐6 to activate the IKK complex. The IKK complex, in turn, reacts with IκB and leads to the activation of NFκB 31. In its dephosphorylated state IκB binds to NFκB in the cytoplasm, preventing it from entering the nucleus for transcription.…”

Section: Discussionmentioning

confidence: 99%

Disruption of VEGF Mediated Flk‐1 Signaling Leads to a Gradual Loss of Vessel Health and Cardiac Function During Myocardial Infarction: Potential Therapy With Pellino‐1

Thirunavukkarasu

Selvaraju

Joshi

et al. 2018

JAHA

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BackgroundThe present study demonstrates that the ubiquitin E3 ligase, Pellino‐1 (Peli1), is an important angiogenic molecule under the control of vascular endothelial growth factor (VEGF) receptor 2/Flk‐1. We have previously reported increased survivability of ischemic skin flap tissue by adenovirus carrying Peli1 (Ad‐Peli1) gene therapy in Flk‐1+/− mice.Methods and ResultsTwo separate experimental groups of mice were subjected to myocardial infarction (MI) followed by the immediate intramyocardial injection of adenovirus carrying LacZ (Ad‐LacZ) (1×109 pfu) or Ad‐Peli1 (1×109 pfu). Heart tissues were collected for analyses. Compared with wild‐type (WTMI) mice, analysis revealed decreased expressions of Peli1, phosphorylated (p‐)Flk‐1, p‐Akt, p‐eNOS, p‐MK2, p‐IκBα, and NF‐κB and decreased vessel densities in Flk‐1+/− mice subjected to MI (Flk‐1+/− MI). Mice (CD1) treated with Ad‐Peli1 after the induction of MI showed increased β‐catenin translocation to the nucleus, connexin 43 expression, and phosphorylation of Akt, eNOS, MK2, and IκBα, that was followed by increased vessel densities compared with the Ad‐LacZ–treated group. Echocardiography conducted 30 days after surgery showed decreased function in the Flk1+/− MI group compared with WTMI, which was restored by Ad‐Peli1 gene therapy. In addition, therapy with Ad‐Peli1 stimulated angiogenic and arteriogenic responses in both CD1 and Flk‐1+/− mice following MI. Ad‐Peli1 treatment attenuated cardiac fibrosis in Flk‐1+/− MI mice. Similar positive results were observed in CD1 mice subjected to MI after Ad‐Peli1 therapy.ConclusionOur results show for the first time that Peli1 plays a unique role in salvaging impaired collateral blood vessel formation, diminishes fibrosis, and improves myocardial function, thereby offering clinical potential for therapies in humans to mend a damaged heart following MI.

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Pellino 1 Is Required for Interleukin-1 (IL-1)-mediated Signaling through Its Interaction with the IL-1 Receptor-associated Kinase 4 (IRAK4)-IRAK-Tumor Necrosis Factor Receptor-associated Factor 6 (TRAF6) Complex

Cited by 163 publications

References 29 publications

The Pellino family: IRAK E3 ligases with emerging roles in innate immune signalling

The Pellino family: IRAK E3 ligases with emerging roles in innate immune signalling

Identification of a TLR4‐ and TRIF‐dependent activation program of dendritic cells

Disruption of VEGF Mediated Flk‐1 Signaling Leads to a Gradual Loss of Vessel Health and Cardiac Function During Myocardial Infarction: Potential Therapy With Pellino‐1

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