<scp>TRAF</scp> trimers form immune signalling networks <i>via</i><scp>RING</scp> domain dimerization

Das, Anubrita; Foglizzo, Martina; Padala, P.; Zhu, Junjie; Day, Catherine L.

doi:10.1002/1873-3468.14530

Cited by 4 publications

(2 citation statements)

References 57 publications

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“…3d). The RING domain confers ubiquitin ligase activity to human TRAF6 24,25 , promoting the assembly of multimeric signaling networks presumably comprised of trimer dimers 26 . In Dictyostelium discoideum, the RING domain recruits TRAF to sites of membrane damage 27 .…”

Section: Trfs Require Each Other For Their Loading To Ciliary Evsmentioning

confidence: 99%

Polycystins recruit cargo to distinct ciliary extracellular vesicle subtypes

Nikonorova,

desRanleau,

Jacobs

et al. 2024

Preprint

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Therapeutic use of tiny extracellular vesicles (EVs) requires understanding cargo loading mechanisms. Here, we used a modular proximity label approach to identify EV cargo associated with the transient potential channel (TRP) polycystin PKD-2 of C. elegans. Polycystins are conserved receptor-TRP channel proteins affecting cilium function; dysfunction causes polycystic kidney disease in humans and mating deficits in C. elegans. Polycystin-2 EV localization is conserved from algae to humans, hinting at an ancient and unknown function. We discovered that polycystins associate with and direct specific cargo to EVs: channel-like PACL-1, dorsal and ventral membrane C-type lectins PAMLs, and conserved tumor necrosis-associated factor (TRAF) signaling adaptors TRF-1 and TRF-2. Loading of these components relied on polycystin-1 LOV-1. Our modular EV-TurboID approach can be applied in both cell- and tissue-specific manners to define the composition of distinct EV subtypes, addressing a major challenge of the EV field.

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Section: Trfs Require Each Other For Their Loading To Ciliary Evsmentioning

confidence: 99%

Polycystins recruit cargo to distinct ciliary extracellular vesicle subtypes

Nikonorova,

desRanleau,

Jacobs

et al. 2024

Preprint

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“…All TRAF members, except for TRAF7, contain a typical C-terminal homology motif known as the TRAF domain, which can couple to other TRAF proteins as well as the cytoplasmic domain of various cellular receptors [7–8]. TRAFs act as intracellular signal transducers and E3 ubiquitin ligases [ 9 ], and are involved in regulating downstream signaling pathways of various cellular receptors, including the TNF receptor superfamily (TNF-R), Toll-like receptors (TLRs), retinoic acid-inducible gene-I receptor (RLRs), NOD-like receptors (NLRs), and cytokine receptors [ 10 – 14 ].…”

Section: Introductionmentioning

confidence: 99%

TRAF inhibition drives cancer cell apoptosis and improves retinoic acid sensitivity in multiple cancers models

et al. 2023

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TNF receptor-associated factors (TRAFs) are signaling adaptor proteins that play a crucial role in regulating cellular receptors’ signaling transduction to downstream pathways and exert multifaceted roles in regulating signaling pathways, cell survival, and carcinogenesis. The 13-cis-retinoic acid (RA), an active metabolite of vitamin A, exhibits anti-cancer properties, but the development of retinoic acid resistance poses a challenge in clinical application. This study aimed to investigate the relationship between TRAFs and retinoic acid sensitivity in various cancers. Here, we revealed that TRAFs’ expression varied significantly across The Cancer Genome Atlas (TCGA) cancer cohorts and human cancer cell lines. Additionally, inhibiting TRAF4, TRAF5, or TRAF6 improved retinoic acid sensitivity and reduced colony formation in ovarian cancer and melanoma cells. Mechanistically, knocking down TRAF4, TRAF5, or TRAF6 in retinoic acid-treated cancer cell lines increased the levels of procaspase 9 and induced cell apoptosis. Further in vivo studies using the SK-OV-3 and MeWo xenograft models confirmed the anti-tumor effects of TRAF knockdown combined with retinoic acid treatment. These findings support that combination therapy with retinoic acid and TRAF silencing may offer significant therapeutic advantages in treating melanoma and ovarian cancers.

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A TRAF-like E3 ubiquitin ligase TrafE coordinates endolysosomal damage response and cell-autonomous immunity toMycobacterium marinum

Raykov

Mottet

Nitschke

et al. 2021

Preprint

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Cells are perpetually challenged by pathogens, protein aggregates or chemicals, that induce plasma membrane or endolysosomal compartments damage. Endolysosomal perforations are recognised as severe stress, however the mechanisms of the cellular response that ensure quality control, repair and endolysosomal homeostasis are just beginning to be unravelled. The endosomal sorting complex required for transport (ESCRT) and the autophagy machinery are recruited to damaged membranes to either repair or to remove membrane remnants. Crucial element of the endolysosomal damage response (ELDR) are factors that sense damage, paralleled by extensive tagging of the damaged organelles with signals, such as ubiquitin, required for the recruitment of ELDR components. Unattended membrane damage leads to leakage of harmful components including protons and reactive oxygen species that cause cell death. To explore ELDR key factors responsible for detection and marking of damaged compartments we use the professional phagocyte Dictyostelium discoideum. We found an evolutionary conserved E3-ligase TrafE that is robustly recruited to intracellular compartments disrupted after infection with Mycobacterium marinum or after sterile damage caused by chemical components. Importantly, we show that the absence of TrafE severely compromises the xenophagy restriction of bacteria as well as autophagy-mediated and ESCRT-mediated ELDR, resulting in early cell death.

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TRAF trimers form immune signalling networks viaRING domain dimerization

Cited by 4 publications

References 57 publications

Polycystins recruit cargo to distinct ciliary extracellular vesicle subtypes

Polycystins recruit cargo to distinct ciliary extracellular vesicle subtypes

TRAF inhibition drives cancer cell apoptosis and improves retinoic acid sensitivity in multiple cancers models

A TRAF-like E3 ubiquitin ligase TrafE coordinates endolysosomal damage response and cell-autonomous immunity toMycobacterium marinum

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