Role of TRAF3 and -6 in the Activation of the NF-κB and JNK Pathways by X-linked Ectodermal Dysplasia Receptor

Sinha, Suwan K.; Zachariah, Sunny; Quiñones, Herson I.; Shindo, Masahisa; Chaudhary, Preet M.

doi:10.1074/jbc.m207923200

Cited by 81 publications

(75 citation statements)

References 44 publications

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“…In addition, we found that XEDAR was a direct transcriptional target of p63, a member of the p53 family, which has an important role in epidermal development (data not shown). However, the evidence obtained so far (Sinha et al, 2002). On the other hand, the EDA-A2/ XEDAR pathway was also shown to promote apoptotic cell death through the DISC (death-inducing signaling complex) formation containing FADD, caspase-8, caspase-10 and c-FLIP (Sinha and Chaudhary, 2004).…”

Section: Discussionmentioning

confidence: 94%

XEDAR as a putative colorectal tumor suppressor that mediates p53-regulated anoikis pathway

et al. 2009

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Colorectal cancers with mutations in the p53 gene have an invasive property, but its underlying mechanism is not fully understood. Through the screening of two data sets of the genome-wide expression profile, one for p53-introduced cells and the other for the numbers of cancer tissues, we report here X-linked ectodermal dysplasia receptor (XEDAR), a member of the TNFR superfamily, as a novel p53 target that has a crucial role in colorectal carcinogenesis. p53 upregulated XEDAR expression through two p53-binding sites within intron 1 of the XEDAR gene. We also found a significant correlation between decreased XEDAR expressions and p53 gene mutations in breast and lung cancer cell lines (P ¼ 0.0043 and P ¼ 0.0122, respectively). Furthermore, promoter hypermethylation of the XEDAR gene was detected in 20 of 20 colorectal cancer cell lines (100%) and in 6 of 12 colorectal cancer tissues (50%), respectively. Thus, the XEDAR expression was suppressed to o25% of surrounding normal tissues in 12 of 18 colorectal cancer tissues (66.7%) due to either its epigenetic alterations and/or p53 mutations. We also found that XEDAR interacted with and subsequently caused the accumulation of FAS protein, another member of p53-inducible TNFR. Moreover, XEDAR negatively regulated FAK, a central component of focal adhesion. As a result, inactivation of XEDAR resulted in the enhancement of cell adhesion and spreading, as well as resistance to p53-induced apoptosis. Taken together, our findings showed that XEDAR is a putative tumor suppressor that could prevent malignant transformation and tumor progression by regulating apoptosis and anoikis.

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Section: Discussionmentioning

confidence: 94%

XEDAR as a putative colorectal tumor suppressor that mediates p53-regulated anoikis pathway

et al. 2009

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“…TRAF6 has been implicated in signaling via several receptors, including RANK (13,14), CD40 (53), IL-1R (18,54,55), TACI (56), BCMA (57), XEDAR (58,59), TROY (60), and CD14 (18). Several of these cytokines and lipopolysaccharide have been shown to induce apoptosis (61)(62)(63)(64).…”

Section: Discussionmentioning

confidence: 99%

Evidence That Receptor Activator of Nuclear Factor (NF)-κB Ligand Can Suppress Cell Proliferation and Induce Apoptosis through Activation of a NF-κB-independent and TRAF6-dependent Mechanism

Bharti

Takada

Shishodia

et al. 2004

Journal of Biological Chemistry

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The receptor activator of NF-B ligand (RANKL), a recently identified member of the tumor necrosis factor (TNF) superfamily, has been shown to induce osteoclastogenesis and dendritic cell survival. Most members of the TNF superfamily suppress cell proliferation and induce apoptosis, but whether RANKL does so is not known. We demonstrate that treatment of monocyte RAW 264.7 cells with RANKL induces dose-dependent growth inhibition (IC 50 ‫؍‬ 10 ng/ml) as determined by dye uptake and Human receptor activator of NF-B ligand (RANKL) 1 (TN-FSF11/TRANCE/OPGL/ODF), a cytokine independently discovered by four different groups (1-4), is a type II transmembrane protein of 317-amino acid length. It belongs to the TNF superfamily and has ϳ30% homology to the TNF-related apoptosis-inducing ligand (TRAIL) and to CD40L and about 20% homology to Fas ligand. It exists in two forms: a 40-to 45-kDa cellular form and a 31-kDa soluble form derived by cleavage of the full-length form at positions

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“…Luciferase Reporter Assays-The NF-B reporter assay was performed essentially as described previously (14). Briefly, MEF cells were transfected in duplicate using LipofectAMINE 2000 (Invitrogen) in a 24-well plate with the various test plasmids along with an NF-B/ luciferase reporter construct (75 ng/well) and a Renilla luciferase reporter construct (phRG-TK; Promega, Madison, WI).…”

Section: Methodsmentioning

confidence: 99%

“…C, increased NF-B transcriptional activity in MFF cells upon transient expression of vFLIP as measured by a luciferase-based reporter assay. MFF (wild type and NIKϪ/Ϫ) cells were transfected with an NF-B/luciferase reporter construct (75 ng/well) and a Renilla reporter construct (75 ng/well), and the experiment was performed as described previously (14). The values shown are the averages of one representative experiment of two in which each transfection was performed in duplicate.…”

Section: Fig 2 Nik Is Not Essential For Vflip K13-induced Nf-b Actimentioning

confidence: 99%

Molecular Genetic Analysis of Human Herpes Virus 8-encoded Viral FLICE Inhibitory Protein-induced NF-κB Activation

Matta

Sun

Moses

et al. 2003

Journal of Biological Chemistry

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Human herpes virus 8 (HHV8), 1 also known as Kaposi's sarcoma-associated herpes virus, is a ␥-2 herpes virus that was originally isolated from Kaposi's sarcoma and has been subsequently associated with several lymphoproliferative disorders, including primary effusion lymphoma or body cavity lymphoma, multicentric Castleman's disease, angioimmunoblastic lymphadenopathy, and some cases of reactive lymphadenopathies (1-3). Although HHV8 encodes for homologs of cytokines, chemokines, and their receptors, none of them is expressed in latently infected primary effusion lymphoma cell lines or Kaposi's sarcoma spindle cells (1). HHV8 also encodes for a protein called K13 (or orf71), which is one of the few viral proteins known to be expressed in cells latently infected with HHV8 and therefore is a prime candidate for causing the cellular transformation associated with infection by this virus (1, 4 -6).HHV8 K13 protein contains two homologous copies of a death effector domain and thus resembles the prodomain of caspase 8 (also known as FLICE). Proteins with two death effector domains have been encountered in other viruses as well and include MC159L and MC169 from the molluscum contagiosum virus and E8 from equine herpes virus 2 (7-9). These virally encoded death effector domain-containing proteins are believed to protect virally infected cells from death receptorinduced apoptosis by blocking the recruitment and/or activation of caspase 8/FLICE (7-9). As a result, these proteins are also collectively known as vFLIPs (viral FLICE inhibitory protein) (7).We have previously demonstrated that HHV8 vFLIP K13 possesses the unique ability to activate the NF-B pathway that is not shared by the vFLIP E8 from equine herpes virus 2 and the vFLIP MC159L from molluscum contagiosum virus (10). We recently demonstrated that vFLIP K13 can co-immunoprecipitate with several protein kinases known to be involved in NF-B activation, such as RIP, NIK, IKK1 (or IKK␣), IKK2 (or IKK␤), and NEMO (or IKK␥) (10, 11). Furthermore, vFLIP K13 was found to physically associate with a ϳ700-kDa I B kinase (IKK) signalsome complex consisting of IKK1, IKK2, and NEMO, which is known to play a crucial role in cytokine-induced NF-B activation (11). In the present study, we have focused on the functional contribution of the above interactions of vFLIP K13 to NF-B activation. MATERIALS AND METHODSPlasmids and Cell Lines-Plasmids containing IKK1, IKK1 kinase mutant, IKK2, IKK2 kinase mutant, and pcDNA3-K13-FLAG have been described previously (10). Wild type, IKK1Ϫ/Ϫ, IKK2Ϫ/Ϫ, and NEMOϪ/Ϫ murine embryonic fibroblast (MEF) cells were obtained from Drs. Inder Verma and Richard Gaynor. Wild type and NIKϪ/Ϫ MEFs have been described previously (12) and were obtained from Dr. Robert Schreiber. These cell lines were cultured in Dulbecco's modified Eagle's medium with 10% fetal calf serum. Wild type and RIP-deficient Jurkat cells were obtained from Dr. Brian Seed and were cultured in RPMI medium supplemented with 10% fetal calf serum (13). Both of these media were supplem...

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Role of TRAF3 and -6 in the Activation of the NF-κB and JNK Pathways by X-linked Ectodermal Dysplasia Receptor

Cited by 81 publications

References 44 publications

XEDAR as a putative colorectal tumor suppressor that mediates p53-regulated anoikis pathway

XEDAR as a putative colorectal tumor suppressor that mediates p53-regulated anoikis pathway

Evidence That Receptor Activator of Nuclear Factor (NF)-κB Ligand Can Suppress Cell Proliferation and Induce Apoptosis through Activation of a NF-κB-independent and TRAF6-dependent Mechanism

Molecular Genetic Analysis of Human Herpes Virus 8-encoded Viral FLICE Inhibitory Protein-induced NF-κB Activation

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