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FLASH GENE

Symbol

TNFSF10

contributors: mct - updated : 25-10-2017

HGNC name	tumor necrosis factor (ligand) superfamily, member 10
HGNC id	11925

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	3q26.31      Physical location : 172.223.298 - 172.241.297
Synonym name	Apo-2 ligand
	TNF-related apoptosis inducing ligand TRAIL
	tumor necrosis factor apoptosis-inducing ligand splice variant delta
	CD253 antigen
	protein TRAIL
Synonym symbol(s)	APO2L, TRAIL, TL2, CD253

DNA

TYPE	functioning gene
STRUCTURE	18.00 kb     5 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
	Binding site   transcription factor
text structure	promoter contains several potential responsive elements, which are associated with different transcription factors

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001190942 3 - 1805 NP_001177871 - 101 - 2000 11095979 NM_003810 5 - 1953 NP_003801 - 281 - 2000 11095979 NM_001190943 2 - 1334 NP_001177872 - 65 - 2000 11095979

EXPRESSION

Type

widely

constitutive of

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Lymphoid/Immune spleen       predominantly Reproductive male system prostate       Respiratory lung

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Lymphoid

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

an extracellular C terminus

conjugated

GlycoP

mono polymer

homomer , trimer

HOMOLOGY

interspecies

homolog to murine Tnfsf10

Homologene

FAMILY

tumor necrosis factor (ligand) superfamily

CATEGORY

signaling cytokine

SUBCELLULAR LOCALIZATION	plasma membrane
text	type II transmembrane glycoprotein

basic FUNCTION	TNF-related apoptosis inducing ligand (TRAIL), independent of DAP3
	inducing appoptosis in the brain
	with TNFRSF10A and TNFRSF10B, play an important role in inflammation
	induces apoptosis through its cognate receptors death receptor TNFRSF10A and TNFRSF10B, preferentially in malignant cells
	promising for anticancer therapy because it induces apoptosis in cancer cells with little or no toxicity to normal cells
	TNFSF10 and CASP8 expression levels were positively correlated with apoptosis in osteosarcoma

CELLULAR PROCESS	cell life, cell death/apoptosis

PHYSIOLOGICAL PROCESS

text	preferentially inducing apoptosis in transformed and tumor cells

PATHWAY

metabolism

signaling

signal transduction

JNK pathway

a component

INTERACTION

DNA

RNA

small molecule

protein	TNFRSF10,triggering the activation of MAPK8/JNK, caspase 8, caspase 3
	APO2L ligand
	CFLAR (is not only a central antiapoptotic modulator of TNFSF10-mediated apoptosis but also an inhibitor of TNFSF10-induced NF-kappaB activation and subsequent proinflammatory target gene expression)
	interacting with PLSCR3 (TNFSF10-induced activation of PKC-delta mediates regulation of the PLSCR3-induced changes in cardiolipin)
	interacting with HOMER1
	CASP4 is involved in induction of apoptosis by TNF-related apoptosis-inducing ligand (TNFSF10) in human melanoma cells
	TRADD plays a survival role in TNFSF10 signaling
	interacting with TRADD (TRADD is critical for resistance to TNFSF10-induced cell death through NFKB activation)
	TNFSF10-mediated tumoricidal activity of macrophages can be stimulated by SERPINF1
	SERPINF1 mediates the induction of TNFSF10 expression by PPARG
	PPP3R1-induced TNFSF10 expression is mediated by NFKB
	interaction of SH3KBP1 with MAP3K4 was increased during the late phase of TNFSF10 incubation, suggesting that sustained MAPK14 and HSPB1 phosphorylation protects cells by preventing further cell death
	TNK2 is required for TNFSF10-induced cell death in multiple epithelial cell lines
	TNFSF10 -induced lysosomal membrane permeabilization is mediated by the multifunctional sorting protein PACS2 and repressed by the E3 ligases BIRC2 and BIRC3
	CTSD enzymatic activity is a new factor affecting sensitivity of breast cancer cells to TNFSF10
	FGF2 was superior, stimulating cell infiltration and angiogenesis better than TNFSF10 and VEGFA
	SPAG6 may regulate apoptosis in SCN4A through the TNFSF10 signal pathway

cell & other

REGULATION

activated by	in response to IFNA, IFNB
	PPARG, that is an activator of TNFSF10 expression in macrophages

repressed by

EGR1

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in low grade astrocytomas, glioblastomas

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer     potential implications for cancer therapy using TNFSF10-receptor agonists cancer     combination of WEE1 inhibitor and TNFSF10 could provide a novel combination for the treatment of basal/triple-negative breast cancer

ANIMAL & CELL MODELS