Novel Toll/IL-1 Receptor Homologous Region Adaptors Act as Negative Regulators in Amphioxus TLR Signaling

Peng, Jian; Tao, Xin; Li, Rui; Hu, Juan; Ruan, Jie; Wang, Ruihua; Yang, Manyi; Yang, Rongliang; Dong, Xiangru; Chen, Shangwu; Xu, Anlong; Yuan, Shaochun

doi:10.4049/jimmunol.1403003

Cited by 13 publications

(5 citation statements)

References 41 publications

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“…Amphioxus SARM plays an inhibitory role in both TICAM- and MyD88-dependent pathways, by interacting with TRAF6, MyD88, and TICAM ( 140 , 141 ). Furthermore, Peng and colleagues found that bbtTIRC inhibits bbtMyD88-mediated signaling by interacting with bbtMyD88 and suppressing bbtTRAF6 polyubiquitination, whereas bbtTIRA inhibits bbtTICAM-mediated activation of NF-κB through interacting with both bbtRIP1b and bbtTICAM ( 142 ). Since genes encoding bbtTIRA and bbtTIRC are NF-κB targets, these two proteins are likely to constitute an effective feedback regulation mechanism of amphioxus NF-κB signaling.…”

Section: Tlrs In Amphioxusmentioning

confidence: 99%

Toll-Like Receptors, Associated Biological Roles, and Signaling Networks in Non-Mammals

et al. 2018

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The innate immune system is the first line of defense against pathogens, which is initiated by the recognition of pathogen-associated molecular patterns (PAMPs) and endogenous damage-associated molecular patterns (DAMPs) by pattern recognition receptors (PRRs). Among all the PRRs identified, the toll-like receptors (TLRs) are the most ancient class, with the most extensive spectrum of pathogen recognition. Since the first discovery of Toll in Drosophila melanogaster, numerous TLRs have been identified across a wide range of invertebrate and vertebrate species. It seems that TLRs, the signaling pathways that they initiate, or related adaptor proteins are essentially conserved in a wide variety of organisms, from Porifera to mammals. Molecular structure analysis indicates that most TLR homologs share similar domain patterns and that some vital participants of TLR signaling co-evolved with TLRs themselves. However, functional specification and emergence of new signaling pathways, as well as adaptors, did occur during evolution. In addition, ambiguities and gaps in knowledge still exist regarding the TLR network, especially in lower organisms. Hence, a systematic review from the comparative angle regarding this tremendous signaling system and the scenario of evolutionary pattern across Animalia is needed. In the current review, we present overview and possible evolutionary patterns of TLRs in non-mammals, hoping that this will provide clues for further investigations in this field.

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Section: Tlrs In Amphioxusmentioning

confidence: 99%

Toll-Like Receptors, Associated Biological Roles, and Signaling Networks in Non-Mammals

et al. 2018

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“…Membrane bound TLR4 recognizes LPS and signals with enhanced efficiency after forming a receptor complex with accessory proteins including myeloid differentiation protein 2 (MD-2), LPS binding protein, and CD14 [11–13]. Docking the LPS-CD14 complex onto the TLR4/MD-2 complex initiates signaling through both the myeloid differentiation primary response 88 (MyD88) and Toll/IL-1 receptor-domain-containing adapter-inducing interferon-β (TRIF) pathways [14]. MyD88-dependent signaling activates nuclear factor-κB (NF-κB) and leads to the production of pro-inflammatory cytokines such as IL-6, tumor necrosis factor α (TNF-α) and IL-12.…”

Section: Introductionmentioning

confidence: 99%

sTLR4/MD-2 complex inhibits colorectal cancer in vitro and in vivo by targeting LPS

et al. 2016

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Colorectal cancer (CRC) is aggressive and associated with TLR4-MD-2 signaling. Toll-like receptor 4 (TLR4) and myeloid differentiation protein 2 (MD-2) were highly expressed in human CRC. The soluble form of extracellular TLR4 domain (sTLR4) and MD-2 may have important roles in binding lipopolysaccharide (LPS). In this study, sTLR4 and MD-2 protein and prepared sTLR4/MD-2 complex were synthesized successfully to restrain LPS-TLR4/MD-2 activation by competing with cellular membrane TLR4 for binding LPS. The sTLR4/MD-2 complex can significantly attenuate LPS induced pro-inflammatory and migration cytokine production in vitro and in vivo, and inhibit the effect of LPS on the cell cycle, migration and invasion of human CRC cells in vitro. Administration of sTLR4/MD-2 complex protected mice from tumor both in xenograft and implantation metastasis model. The sTLR4/MD-2 complex treated mice had smaller tumor, less body weight loss and lower expression of inflammatory cytokines. Here, the azoxymethane/dextran sulfate sodium salt (AOM/DSS) murine model was used as an experimental platform to simulate the physiological and pathological processes of cancers associated with chronic intestinal inflammation. AOM/DSS-induced tumors were inhibited in mice treated by sTLR4/MD-2 complex. It is demonstrated in our study that sTLR4/MD-2 complex could inhibit CRC by competing with binding LPS, raising the complex's possibility of a new prevention agent against CRC.

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“…Jalview was used for editing and viewing sequence alignments (62). The transmembrane regions of Aeg1 were predicted by the SMART Web site (63) .…”

Section: Methodsmentioning

confidence: 99%

A unique cell division protein critical for the assembly of the bacterial divisome

Chu

Wang

Zhu

et al. 2023

Preprint

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Identification of novel essential bacterial genes is important for not only the understanding of their cell biology but also the development of new antimicrobials. Here we report a previously unrecognized core component of the Acinetobacter baumannii divisome. Our results reveal that the protein, termed Aeg1 interacts with multiple cell division proteins, including FtsN, which is required for components of the divisome to localize to the midcell. We demonstrate that the FtsAE202K and FtsBE65A mutants effectively bypassed the need of Aeg1 by A. baumannii, so did the activation variants FtsWM254I and FtsWS274G. Our results suggest that Aeg1 is a cell division protein that arrives at the division site to initiate cell division by recruiting FtsN, which activates FtsQLB and FtsA to induces the septal peptidoglycan synthase FtsWI. The discovery of the new essential cell division protein has provided a new target for the development of antibacterial agents.

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Novel Toll/IL-1 Receptor Homologous Region Adaptors Act as Negative Regulators in Amphioxus TLR Signaling

Cited by 13 publications

References 41 publications

Toll-Like Receptors, Associated Biological Roles, and Signaling Networks in Non-Mammals

Toll-Like Receptors, Associated Biological Roles, and Signaling Networks in Non-Mammals

sTLR4/MD-2 complex inhibits colorectal cancer in vitro and in vivo by targeting LPS

A unique cell division protein critical for the assembly of the bacterial divisome

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