Induction of cell death by tumour necrosis factor (TNF) receptor 2,CD40 and CD30: a role for TNF-R1 activation by endogenous membrane-anchored TNF

Grell, Matthias

doi:10.1093/emboj/18.11.3034

Cited by 267 publications

(225 citation statements)

References 57 publications

Supporting

Mentioning

209

Contrasting

Unclassified

Order By: Relevance

“…However, XEDAR lacks a discernible death domain; the molecular mechanism of XEDAR-induced apoptosis was not well understood. Some TNFR members that lacked the death domain were shown to induce apoptosis through the interaction with FAS, another p53-inducible TNFR superfamily member (Afford et al, 1999;Grell et al, 1999). Similarly, our result suggested that XEDAR promoted apoptotic signaling through the interaction with FAS.…”

Section: Discussionsupporting

confidence: 63%

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

et al. 2009

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 63%

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

et al. 2009

View full text Add to dashboard Cite

show abstract

“…Grell et al [39] propose a model according to which DD-lacking receptors, like TNFR2, are coupled to the cell death machinery and can indirectly induce cell death through inducing endogenous membrane-anchored TNF, that can then signal through the DDcontaining TNFR1 and induce apoptosis. Others suggest a socalled ''ligand-passing'' mechanism by which TNFR2 binds TNF and allows an increased concentration of TNF to be passed on to TNFR1 to activate the apoptotic machinery [14].…”

Section: Discussionmentioning

confidence: 99%

Lack of TNFR2 expression by CD4⁺ T cells exacerbates experimental colitis

et al. 2009

View full text Add to dashboard Cite

TNF plays fundamental roles in the induction and perpetuation of inflammation. The effects of TNF are mediated through TNF receptor (TNFR) 1 or 2. As these two receptors mediate different functions, selective targeting of one receptor may represent a more specific treatment for inflammatory disorders than the complete blocking of TNF. TNFR2 expression is up-regulated in inflammatory bowel disease. Hence, we directly assessed the role of TNFR2 signaling in the CD4 + T-cell transfer model of colitis using TNFR2 À/À or WT mice as donors of colitogenic CD4 + CD45RB hi T cells for transfer into syngeneic RAG2 À/À or RAG2 À/À TNFR2 À/À recipient mice. Although the absence of TNFR2 expression by nonlymphoid cells of the recipient mice does not influence the course of colitis, transfer of TNFR2 À/À CD4 + T cells leads to an accelerated onset of disease and to more severe signs of inflammation. The enhanced colitogenic potential of TNFR2 À/À CD4 1 T cells is associated with reduced activation-induced cell death, resulting in an increased accumulation of TNFR2 À/À CD4 1 T cells. Hence, TNFR2 signaling is crucial for the TNF-dependent contraction of the disease-inducing T cells. Therefore, a selective blocking of TNFR2 may lead to exacerbation rather than attenuation of T-cell-mediated inflammatory disorders.Key words: CD4 1 T cells Á Inflammation Á Intestinal immunity Á TNF Introduction TNF plays a fundamental role in immunity and inflammation based on its pleiotropic effects on differentiation, growth and apoptotic cell death of both immune and non-immune cell subsets [1,2]. It is well established that TNF is also critically involved in the pathogenesis of inflammatory and autoimmune diseases such as rheumatoid arthritis, MS and inflammatory bowel diseases (IBD) [3]. Monocytes and macrophages are the main producers of TNF, but T and B lymphocytes and also mast cells can produce significant amounts of TNF. Interestingly, intestinal cell lines are induced to synthesize TNF upon infection with invasive bacterial strains [4]. TNF mediates its functions by binding as a trimer to either TNF receptor (TNFR) 1 or 2. The binding of TNF trimer to the preassembled TNFR complex leads to conformational changes of the receptors facilitating signal transduction through rapid recruitment of downstream signaling molecules. Both receptors have distinct signal transduction pathways and mediate distinct cellular responses [1,[5][6][7][8][9][10]. The 55 kDa receptor, TNFR1 (also known as p55, p60, TNFRSF1a, CD120a) is expressed on most cell types. The intracellular domain of TNFR1 contains a death domain (DD) that leads to apoptosis through caspase activation. TNFR1 signaling can also mediate transcription of anti-apoptotic proteins, inflammatory cytokines and chemokines through activation of NF-kB. The 75 kDa receptor, TNFR2 (also known as p75, p80, TNFRSF1b, CD120b), is Eur. J. Immunol. 2009. 39: 1743-1753 DOI 10.1002 Cellular immune response 1743 expressed predominantly by haematopoietic cells, but expression by other cell types can be i...

show abstract

“…Since CD40 belongs to the TNF receptor superfamily that triggers apoptosis by caspase-8 activation (Ashkenazi and Dixit, 1998;Grell et al, 1999;Eliopoulos et al, 2000), experiments were performed in which CD40L-induced apoptosis of ACN cells was investigated in the presence or absence of Z-LETD-FMZ, a selective inhibitor of caspase-8 (Ahmad and Shi, 2000). It was found that apoptosis of CD40 þ ACN cells cultured with CD40L was abrogated by Z-LETD-FMZ, thus pointing to the involvement of caspase-8 in our experimental model.…”

Section: Discussionmentioning

confidence: 86%

“…Apoptosis of CD40+ NB cells induced by CD40L is caspase-8 dependent CD40 belongs to the TNF receptor superfamily, whose components trigger cell apoptosis through caspase-8 activation (Ashkenazi and Dixit, 1998;Grell et al, 1999;Eliopoulos et al, 2000). We therefore investigated whether this mechanism operated also in CD40-expressing NB cells.…”

Section: Cd40l Triggers Apoptosis Of Nb Cells Expressing Surface Cd40mentioning

confidence: 99%

Expression of costimulatory molecules in human neuroblastoma. Evidence that CD40+ neuroblastoma cells undergo apoptosis following interaction with CD40L

et al. 2003

View full text Add to dashboard Cite

Tumour cells display low to absent expression of costimulatory molecules. Here, we have investigated the expression of costimulatory molecules (CD40, CD80, CD86, PD-1L, B7H2, OX40L and 4-1BBL) in human neuroblastoma (NB) cells, since virtually no information is available on this issue. Both established NB cell lines and primary tumours were tested by RT -PCR and flow cytometry. Neuroblastoma cell lines expressed the transcripts of all costimulatory molecule genes, but not the corresponding proteins. Culture of NB cell lines with human recombinant (r)IFN-g induced surface expression of CD40 in half of them. Primary NB cells showed CD40, CD80, CD86, OX40L, 4-1BBL, but not PD-1L and B7H2, mRNA expression. Surface CD40 was consistently detected on primary NB cells by flow cytometry. Interferon-g gene-transfected NB cells expressed constitutively surface CD40 and were induced into apoptosis by incubation with rCD40L through a caspase-8-dependent mechanism. CD40 may represent a novel therapeutic target in NB.

show abstract

Induction of cell death by tumour necrosis factor (TNF) receptor 2,CD40 and CD30: a role for TNF-R1 activation by endogenous membrane-anchored TNF

Cited by 267 publications

References 57 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

Lack of TNFR2 expression by CD4⁺ T cells exacerbates experimental colitis

Expression of costimulatory molecules in human neuroblastoma. Evidence that CD40+ neuroblastoma cells undergo apoptosis following interaction with CD40L

Contact Info

Product

Resources

About

Induction of cell death by tumour necrosis factor (TNF) receptor 2,CD40 and CD30: a role for TNF-R1 activation by endogenous membrane-anchored TNF

Cited by 267 publications

References 57 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

Lack of TNFR2 expression by CD4+ T cells exacerbates experimental colitis

Expression of costimulatory molecules in human neuroblastoma. Evidence that CD40+ neuroblastoma cells undergo apoptosis following interaction with CD40L

Contact Info

Product

Resources

About

Lack of TNFR2 expression by CD4⁺ T cells exacerbates experimental colitis