MYCN directly associated with its regulatory motif (E-box) within the putative BIRC7 promoter
MAPPING
cloned
Y
linked
N
status
provisional
RNA
TRANSCRIPTS
type
messenger
text
cleaved by effector caspases to produce a truncated form with paradoxical pro-apoptotic activity (PMID: 17294084)
identification
nb exons
type
bp
product
Protein
kDa
AA
specific expression
Year
Pubmed
7
-
1268
-
280
detected in some fetal and adult tissues and in the majority of livin-expressing tumors
2007
17294084
also called variant 2/isoform beta or livin beta
lacking the coiled coil
protection from apoptosis initiated by etoposide
truncated Livin (tLivin) is found in a peri-nuclear distribution with marked localization to the Golgi apparatus
having an intact RING domain enabling its pro-apoptotic function
7
splicing
1322
39
298
detected in some fetal and adult tissues and in the majority of livin-expressing tumors
2007
17294084
also called variant 1 or KIAP livin alpha
protection from apoptosis induced by staurosporin
promote cell proliferation by regulating G(1)-S cell cycle transition and possibly play an important part in initiation of prostate cancer (PMID: 20607788)
promotes tumor initiation in comparison with control (PMID: 19549891)
-
-
-
-
-
subcellular localization of tLivin was mainly restricted to the cytoplasm
2009
19549891
BIRC7 specifically cleaved by caspases to produce a truncated protein with paradoxical proapoptotic activity (tLivin)
exerted a pro-apoptotic effect on cells
BIRC7 plays a major role in tumorigenicity and NK cells induce cleavage of BIRC7 to its proapoptotic truncated protein that in turn inhibits tumor growth
full-length BIRC7 shows diffuse cytoplasmic localization, truncated form is found in a peri-nuclear distribution with marked localization to the Golgi apparatus
basic FUNCTION
involved in the regulation of apoptosis
important determinant for the apoptotic resistance of non-small cell lung cancer cells
may exert anti-apoptotic action by activating JNK1 signaling pathway and inhibiting caspase-3 activation
may contribute to drug resistance in neuroblastoma, and may be essential for survival of some cancer cells
has a role in thrombopoiesis by regulating the apoptotic and antiapoptotic balance in megakaryocyte endoreplication and platelet production
BIRC7,CASP3, BIRC5 are closely related to the occurrence and development of prostatic cancer
CELLULAR PROCESS
cell life, antiapoptosis
PHYSIOLOGICAL PROCESS
PATHWAY
metabolism
signaling
a component
INTERACTION
DNA
RNA
small molecule
protein
inhibitor of downstream caspase, CASP9 (strong), CASP3 (weak) and CASP7
can act as an E3 ubiquitin ligase for targeting the degradation of Smac/DIABLO (exhibits E3 ubiquitin ligase activity to degrade the pivotal apoptotic regulator Smac/DIABLO through the ubiquitin-proteasome pathway)
new, BIRC7-dependent, apoptotic role for TEAD1
cell & other
REGULATION
activated by
MYCN (MYCN protein may act as a transcriptional activator of BIRC7 expression supporting the notion that, in cells co-expressing these genes, the antiapoptotic effect of BIRC7 may counteract the apoptotic effects associated with MYCN amplification)
induced by
various stimuli
repressed by
Smac/DIABLO
Other
cleaved by effector caspases to produce a truncated form with paradoxical pro-apoptotic activity
ASSOCIATED DISORDERS
corresponding disease(s)
Other morbid association(s)
Type
Gene Modification
Chromosome rearrangement
Protein expression
Protein Function
tumoral
 
 
--over
 
in a significant portion of non-small cell lung cancer
tumoral
 
 
--over
 
in renal cell carcinoma
tumoral
 
 
--over
 
protect tumor cells of neuroblastoma with amplified MYCN oncogene from genotoxic agents
tumoral
 
 
--over
 
significantly higher in pancreatic ductal adenocarcinoma, than that in peritumoral tissue, benign pancreatic lesions, and normal pancreatic tissue
tumoral
 
 
--over
 
is specifically over-expressed in adrenocortical carcinoma (ACC)
Susceptibility
Variant & Polymorphism
Candidate gene
Marker
BIRC7 upregulation might serve as a valuable biomarker of increased recurrence risk in advanced T stages and medium-grade prostate cancer
new molecular marker of adrenocortical carcinoma (ACC)
livin expression could be a novel prognostic marker in childhood ALL
Therapy target
System
Type
Disorder
Pubmed
cancer
brain
therapeutic targeting of BIRC7 to block its antiapoptotic effect in neuroblastoma
cancer
BIRC7 cleavage will become a highly potent proapoptotic agent, and a novel strategy for cancer therapy