Apoptosis Database

Description [+]

Synonyms: TNFRSF23, TUMOR NECROSIS FACTOR RECEPTOR SUPERFAMILY MEMBER 23, MDCTRAILR1, MSOB, TNFRH1
Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Rodentia; Mus musculus
Short gene description: Tumor necrosis factor receptor superfamily member 23 Precursor (Tumor necrosis factor receptor p60 homolog 1)(TNF receptor family member SOB)(Decoy TRAIL receptor 1)(TNF receptor homolog 1) [Source:UniProtKB/Swiss-Prot;Acc:Q9ER63]
Family: Death receptor
Process: undefined,
Pathways: undefined,
Criteria: manually curated
Curator comment:
WIKI: TNFRSF23-M_musculus

References [+]

TRAIL-R deficiency in mice promotes susceptibility to chronic inflammation and tumorigenesis.
Finnberg N, Klein-Szanto AJ, El-Deiry WS
Preclinical data support the potential of the death-signaling receptors for TRAIL as targets for cancer therapy. However, it is unclear whether these death-signaling receptors suppress the emergence and growth of malignant tumors in vivo. Herein we show that TNF-related apoptosis-inducing ligand receptor (TRAIL-R), the only proapoptotic death-signaling receptor for TRAIL in the mouse, suppresses inflammation and tumorigenesis. Loss of a single TRAIL-R allele on the lymphoma-prone Emu-myc genetic background significantly reduced median lymphoma-free survival. TRAIL-R-deficient lymphomas developed with equal frequency irrespective of mono- or biallelic loss of TRAIL-R, had increased metastatic potential, and showed apoptotic defects relative to WT littermates. In addition, TRAIL-R-/- mice showed decreased long-term survival following a sublethal dose of ionizing radiation. Histological evaluation of moribund irradiated TRAIL-R-/- animals showed hallmarks of bronchopneumonia as well as tumor formation with increased NF-kappaB p65 expression. TRAIL-R also suppressed diethylnitrosamine-induced (DEN-induced) hepatocarcinogenesis, as an increased number of large tumors with apoptotic defects developed in the livers of DEN-treated TRAIL-R-/- mice. Thus TRAIL-R may function as an inflammation and tumor suppressor in multiple tissues in vivo. J Clin Invest. 2008 Jan;118(1):111-23.

Molecular cloning and functional analysis of the mouse homologue of the KILLER/DR5 tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptor.
Wu GS, Burns TF, Zhan Y, Alnemri ES, El-Deiry WS
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptors are members of the tumor necrosis factor superfamily. TRAIL selectively kills cancer cells but not normal cells. We report here the cloning of the mouse homologue of the TRAIL receptor KILLER/DR5 (MK). The cDNA of MK is 1146 bp in length and encodes a protein of 381 amino acids. MK contains an extracellular cysteine-rich domain, a transmembrane domain, and a cytoplasmic death-domain characteristic of Fas, tumor necrosis factor, and human TRAIL receptors. MK is highly homologous and binds TRAIL with similar affinity as human DR4 and KILLER/DR5. MK induces apoptosis in mouse and human cells and inhibits colony growth of NIH3T3 cells. Expression of MK is p53-dependent and up-regulated by tumor suppressor p53 and by DNA damaging agents in mouse cells undergoing apoptosis. This is the first report describing a mouse TRAIL receptor gene and also demonstrating that the p53-dependent regulation of KILLER/DR5-mediated apoptosis is conserved between human and mouse. Cancer Res. 1999 Jun 15;59(12):2770-5.

Identification of a new murine tumor necrosis factor receptor locus that contains two novel murine receptors for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).
Schneider P,Olson D,Tardivel A,Browning B,Lugovskoy A,Gong D,Dobles M,Hertig S,Hofmann K,Van Vlijmen H,Hsu YM,Burkly LC,Tschopp J,Zheng TS
Tumor necrosis factor (TNF) ligand and receptor superfamily members play critical roles in diverse developmental and pathological settings. In search for novel TNF superfamily members, we identified a murine chromosomal locus that contains three new TNF receptor-related genes. Sequence alignments suggest that the ligand binding regions of these murine TNF receptor homologues, mTNFRH1, -2 and -3, are most homologous to those of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors. By using a number of in vitro ligand-receptor binding assays, we demonstrate that mTNFRH1 and -2, but not mTNFRH3, bind murine TRAIL, suggesting that they are indeed TRAIL receptors. This notion is further supported by our demonstration that both mTNFRH1:Fc and mTNFRH2:Fc fusion proteins inhibited mTRAIL-induced apoptosis of Jurkat cells. Unlike the only other known murine TRAIL receptor mTRAILR2, however, neither mTNFRH2 nor mTNFRH3 has a cytoplasmic region containing the well characterized death domain motif. Coupled with our observation that overexpression of mTNFRH1 and -2 in 293T cells neither induces apoptosis nor triggers NFkappaB activation, we propose that the mTnfrh1 and mTnfrh2 genes encode the first described murine decoy receptors for TRAIL, and we renamed them mDcTrailr1 and -r2, respectively. Interestingly, the overall sequence structures of mDcTRAILR1 and -R2 are quite distinct from those of the known human decoy TRAIL receptors, suggesting that the presence of TRAIL decoy receptors represents a more recent evolutionary event. J Biol Chem. 2003 Feb 14;278(7):5444-54. Epub 2002 Dec 3.

Following TRAILs path in the immune system.
Falschlehner C,Schaefer U,Walczak H
The members of the tumour necrosis factor (TNF) superfamily of cytokines play important roles in the regulation of various immune-cell functions. Likewise, induction of cell death by apoptosis is indispensable for the normal functioning of the immune system. There are two major pathways of apoptosis induction. The intrinsic, or mitochondrial, pathway is regulated by the activation and interaction of members of the Bcl-2 family. The extrinsic, or death receptor, pathway is triggered by certain TNF family members when they engage their respective cognate receptors on the surface of the target cell. Hence, cell-to-cell-mediated death signals are induced by activation of these death receptor-ligand systems. Besides TNF itself and the CD95 (Fas/APO-1) ligand (FasL/Apo1L), the TNF-related apoptosis-inducing ligand (TRAIL/Apo2L) belongs to the subfamily of ligands that is responsible for extrinsic induction of cell death. Depending on their status of stimulation, TRAIL can be expressed by various cells of the immune system, amongst them natural killer (NK) cells, T cells, natural killer T cells (NKT cells), dendritic cells and macrophages. TRAIL has been implicated in immunosuppressive, immunoregulatory and immune-effector functions. With respect to pathological challenges, TRAIL and its receptors have been shown to play important roles in the immune response to viral infections and in immune surveillance of tumours and metastases. In this review we summarize the current knowledge on the role of TRAIL and its receptors in the immune system and, based on this, we discuss future directions of research into the diverse functions of this fascinating receptor-ligand system. Immunology. 2009 Jun;127(2):145-54.

Structure & Sequence [+]

Source	Domain Name	Start	End
PFAM A	TNFR_c6	75	114
PFAM A	TNFR_c6	116	155

Evolution [+]

Gene Ontology [+]

GO id	Name	Ontology type	Evidence
GO:0015833	peptide transport	biological_proccess	IEA
GO:0004872	receptor activity	mollecular_function	IEA
GO:0005515	protein binding	mollecular_function	IPI
GO:0005524	ATP binding	mollecular_function	IEA
GO:0015197	peptide transporter activity	mollecular_function	IEA
GO:0005886	plasma membrane	cell_component	IEA
GO:0031225	anchored to membrane	cell_component	IEA
GO:0016020	membrane	cell_component	IEA

Curated Isoforms [+]

Transcript	Translation
OTTMUST00000058457 *	OTTMUSP00000028319 *
OTTMUST00000058458	OTTMUSP00000028320

Information from other databases [+]

Gene related links:

Gene info from MGI [?] MGI:1930269
Ensembl genome browser [?] : ENSMUSG00000037613
Expression info from Arrayexpress [?] : ENSMUSG00000037613
Protein expression from Protein Atlas: [?] ENSMUSG00000037613
Community gene edition from Wikigenes: [?] 79201

Protein related links:

Uniprot protein info: Q9ER63
PIR protein info: Q9ER63
Protein interactions from IntAct: Q9ER63

Other links

entrezgene: 79201
refseq_dna: NM_024290
refseq_peptide: NP_077252

Click on [?] for more information.

TNFRSF23 (Mus musculus)