Role of membrane microdomain rafts in TNFR-mediated signal transduction

Hueber, Anne-Odile

doi:10.1038/sj.cdd.4401155

Cited by 43 publications

(37 citation statements)

References 24 publications

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“…In fact, recent studies indicate that activated receptors of the TNFR family were accumulated as oligomers in subdomains of the cytoplasmic membrane component termed lipid RAFTs (Hueber, 2003). Likewise, recent studies showed that enforced LMP1 recruitment into lipid rafts is essential and sufficient to promote signaling, whereas the role of the trimerization of this protein is a matter of debate (Kaykas et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

A novel dominant-negative mutant form of Epstein–Barr virus latent membrane protein-1 (LMP1) selectively and differentially impairs LMP1 and TNF signaling pathways

et al. 2004

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The latent membrane protein-1 (LMP1) is an integral membrane molecule expressed by Epstein-Barr virus (EBV) during viral latency and displays properties of a constitutively activated member of the TNF receptor family. LMP1 is required for B-cell or monocyte immortalization induced by EBV and is sufficient to transform rodent fibroblasts. Transforming potential of LMP1 is mediated by its cytoplasmic C-terminal domain, which activates various cellular signaling pathways including NFjB and JNK. In this report, we constructed mutants of LMP1 with preserved membrane spanning domain but mutated in the C-terminal domain and a second truncated C-terminal LMP1 fused to the enhanced green fluorescent protein. This latter mutant, termed LMP1-CT, impairs signaling by ectopic LMP1 as well as endogenous EBVexpressed wild-type (wt) LMP1. In contrast to dominantnegative mutants of LMP1 with preserved membrane spanning domains, LMP1-CT was unable to bind wt LMP1 to form an inactive complex. Its dominant-negative effects were due to binding and sequestration of LMP1 adapters TRAF2 and TRADD as assessed by coimmunoprecipitation experiments and confocal analysis. The effect was selective since LMP1-CT did not inhibit IL1b-induced signaling, whereas it impaired TNF-triggered NFjB and JNK signals without affecting TNF-induced apoptosis. In addition and in contrast to LMP1 constructs with membrane localization, LMP-CT did not display cytostatic properties in noninfected cells. Importantly, LMP1-CT inhibited survival induced by LMP1 in an EBV-transformed T-cell line expressing the type II viral latency commonly found in the majority of EBVassociated human tumors. These data demonstrate that LMP1-CT is a new tool to explore the differences between LMP1 and TNF signaling and may facilitate the design of molecules with potential therapeutic roles.

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Section: Discussionmentioning

confidence: 99%

A novel dominant-negative mutant form of Epstein–Barr virus latent membrane protein-1 (LMP1) selectively and differentially impairs LMP1 and TNF signaling pathways

et al. 2004

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“…Instead, signaling is achieved by recruitment of intracellular adapter molecules that associate with the cytoplasmic tail of the TNF-R in a signal-dependent manner (Figure 6a). The recruitment of TNF-R1 to membrane microdomains, referred to as lipid rafts, with subsequent assembly of the signaling complex, is necessary for signaling to NF-kB and prevention of apoptosis (Hueber, 2003;Legler et al, 2003). Ligation of TNF-R1 by trimeric TNFa causes aggregation of the receptor allowing binding of the TNF-R-associated death domain protein (TRADD).…”

Section: Tnf-r Superfamily Signalingmentioning

confidence: 99%

NF-κB and the immune response

2006

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“…In addition, palmitoylation and lipid raft localization were reported to be a prerequisite for DCC proapoptotic activity, both in vitro and in primary commissural neurons (Furne et al, 2006). Lipid rafts are ordered membrane microdomains enriched in sphingolipids and cholesterol, and are proposed to have an important role in cell signaling, in particular through the organization of surface receptors, signaling enzymes and adaptor molecules into complexes at specific sites in the membrane (Simons and Toomre, 2000;Hueber, 2003). It was then shown that DCC presence in lipid rafts is required to allow caspase-9/DCC interaction, suggesting that this caspase-activating complex occurs in and takes advantage of lipid rafts.…”

Section: Proapoptotic Signaling By Drsmentioning

confidence: 99%

Dependence receptors: a new paradigm in cell signaling and cancer therapy

2010

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Dependence receptors (DRs) now form a family of more than a dozen membrane receptors that are not linked by their structure, but by common functional traits. The most notable is their ability to trigger two opposite signaling pathways: in the presence of ligand, these receptors activate classic signaling pathways implicated in cell survival, migration and differentiation. In the absence of ligand, they do not stay inactive, rather they elicit an apoptotic signal. Thus, cells expressing this kind of receptor are dependent on the presence of ligand in the extracellular environment to survive. This review will recapitulate the increasing data regarding the molecular mechanisms associated with DRs, their potential implication during development, as well as their deregulation during tumorigenesis and, finally, their emergence as new possible therapeutic targets for cancer treatment.

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Role of membrane microdomain rafts in TNFR-mediated signal transduction

Cited by 43 publications

References 24 publications

A novel dominant-negative mutant form of Epstein–Barr virus latent membrane protein-1 (LMP1) selectively and differentially impairs LMP1 and TNF signaling pathways

A novel dominant-negative mutant form of Epstein–Barr virus latent membrane protein-1 (LMP1) selectively and differentially impairs LMP1 and TNF signaling pathways

NF-κB and the immune response

Dependence receptors: a new paradigm in cell signaling and cancer therapy

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