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FLASH GENE

Symbol

DIABLO

contributors: mct/ - updated : 04-06-2015

HGNC name	diablo homolog (Drosophila)
HGNC id	21528

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type	ubiquitous

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 Cardiovascular heart       highly Digestive liver       highly Lymphoid/Immune spleen         Reproductive female system ovary     highly   male system testis     highly   male system prostate     highly Urinary kidney       highly

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

mono polymer

homomer , dimer

isoforms

Precursor

HOMOLOGY

interspecies	homolog to murine Diablo (85.2pc)
	homolog to rattus Diablo (85.7pc)

Homologene

FAMILY

CATEGORY

regulatory

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,mitochondria,interspace
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,cytosolic
text	released from mitochondria at entering the cytosol during apoptosis triggered by UV or gamma irradiation, cytotoxic drugs and DNA damage

basic FUNCTION	promoting apoptosis by binding to caspase inhibitors of the IAP family (BIRCS) and preventing them from inhibiting caspases
	activating caspases in the cytochrome C/APAF1/CASP9 pathway
	involved in TNF-mediated CASP8 activation and apoptosis
	playing an essential role in the apoptosis induced by non-steroidal anti-inflammatory drugs in colon cancer
	IAP-binding protein that is released from mitochondria during apoptosis
	potentiating apoptosis by simultaneously antagonizing caspase-IAP interactions and repressing IAP ubiquitin ligase activities
	one of the proapoptotic proteins released from the mitochondria that inactivate IAPs and play a redundant role during development and cell death
	play an obligatory role in the tumor cells during several pathways of apoptosis induction
	mitochondrial apoptogenic protein, mediating the proapoptotic function of BBC3 by regulating BBC3-induced mitochondrial events
	playing an important role in executing DNA damage-induced and BBC3-mediated apoptosis and can participates in a feedback amplification loop to promote cytochrome c release and other mitochondrial events in apoptosis
	can target BIRC2 to induce TNFalpha-dependent apoptosis and so may have a role in treating cancer
	DIABLO function, but not Caspase-9 activity, was decisive for full effector caspase activation and clonogenic execution of Type I cells
	acing potentially to enhance the early phase executioner caspase activity through the modulation of inhibitory interactions between specific IAP family members and executioner CASP3 and CASP7
	plays key roles in both the diagnosis and treatment of cancer, especially lung cancer
	in addition to APAF1 or apoptosome formation, DIABLO is also essential for MTCH1-induced apoptosis

CELLULAR PROCESS	cell life, cell death/apoptosis

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	directly binding to the BIR domain of IAPs (XIAP and others) nad interacting with CASP9
	TNF, MAPK8, BID, CASP8 for TNF-induced apoptosis
	interacting with UBE2K (promoted degradation of mature DIABLO through the ubiquitin proteasome pathway)
	PRPS1 initiates caspase activation upstream of cytochrome C and DIABLO
	inhibits apoptosis of breast cancer cells by suppression of BIRC5
	in apoptosis, BIRC5 recognize the DIABLO protein
	BIRC6 may have a potential oncogenic role in neuroblastoma by inactivating cytoplasmic DIABLO
	AREL1 interacted with and ubiquitinated IAP antagonists such as DIABLO, HTRA2, and PRPS1
	IRF1 is critical dual regulator of DIABLO mimetic-induced apoptosis and inflammatory cytokine response
	intramembrane cleavage of DIABLO by PARL generates an N-terminal IAP-binding motif, which is required for its apoptotic activity

cell & other

REGULATION

activated by

caspases

inhibited by

BCL2

ASSOCIATED DISORDERS

corresponding disease(s)

DFNA64

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral   deletion     in mycosis fungoides (MF), the most frequent form of cutaneous T cell lymphoma constitutional     --low   alters both caspase-dependent and caspase-independent intrinsic programmed cell death

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer     DIABLO mimetics can elicit a proinflammatory cell death that is sufficient to activate adaptive antitumor immune responses in cancer

ANIMAL & CELL MODELS