Atlas of Genetics and Cytogenetics in Oncology and Haematology


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Abstract

Abstract The BIRC6 gene (BRUCE/APOLLON) encodes the cytoplasmic protein BIRC6 in mammals, consisting of a single N-terminal baculoviral IAP repeat (BIR) domain and a C-terminal ubiquitin-conjugating (UBC) domain. Of the huge protein size at 528 kDa, BIRC6 demonstrated pleiotropic functions including inhibition of apoptosis, cytoprotection, regulation of cytokinesis, mitosis, autophagy and neutrophil differentiation. With the BIR domain, BIRC6 is defined as a member of the Inhibitor of Apoptosis (IAP) family. Through its BIR domain, BIRC6 binds to active caspases, including caspases-3, 6, 7 and 9 and accounts for its ability to inhibit the caspase cascade and ultimately apoptosis. The UBC domain has chimeric E2/E3 ubiquitin ligase activity where it facilitates proteosomal degradation of various proteins, including pro-apoptotic proteins p53, caspases, Smac and mitotic regulator cyclin A. More importantly, the UBC domain plays an indispensable role in embryonic development in mammals and spermatogenesis in Drosophila. Increasing evidence supports the cancer promoting role of BIRC6. Elevated BIRC6 expression has been found in a variety of cancers and was shown to contribute to treatment resistance.

BIRC6 (Baculoviral IAP repeat-containing 6)

Identity

Other namesAPOLLON
BRUCE
HGNC (Hugo) BIRC6
LocusID (NCBI) 57448
Location 2p22.3
Location_base_pair Starts at 32582096 and ends at 32843965 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Local_order - CARD12 (caspase recruitment domain family member 12) (encoded on minus strand, 32303029-32344427)
- YIPF4 (YIP1 domain family member 4) (32356483-32385159)
- BIRC6 (32435234-32697467)
- TTC27 (tetratricopeptide repeat domain 27) (32706633-32899620)
- LTBP1 (latent transforming growth factor beta binding protein 1) (33025896-33478077)

DNA/RNA

Description The BIRC6 gene comprises 75 exons resulting in a transcript of 16066 bps. The ATG is in the first exon.
Transcription Only one variant of BIRC6 has been found so far which comprises 14490 bps. There are several synonymous and nonsynonymous SNPs reported for BIRC6 (E589K, L1742F, R2187T, T2646S, T3708N, E3864K, Q4323H, N4324Y, S4325C, N4326T, P4329R).
Pseudogene Not known. There is evidence for a processed pseudogene in M. musculus.

Protein

 
  BIRC6 is a component of the apoptosis regulatory network. Multiple protein-protein interactions allow a switch from apoptosis inhibition to inactivation in later steps in apoptosis. BIRC6's action on activated caspases and other pro-apoptotic molecules might be restricted to the trans-Golgi network and the vesicular system.
Description BIRC6 contains two functionally validated domains: A N-terminal BIR repeat (SMART SM00238, aa: 256-332) and a C-terminal UBC domain (SMART SM00212, aa: 4548 - 4712). The BIR repeat is needed for interactions with caspases and IAP-binding motif (IBM) containing proteins (HtrA2, Smac). The UBC domain can form a thiolester linkage with ubiquitin transferred by E1.
Between aa 1589-1633 a coiled-coil region can be found.
Expression BIRC6 is highly expressed in brain, testis, lymphatic cells and secretory organs and also found in any other tissues (Hauser et al., 1998). It is highly expressed in the mouse embryos up to E11 and then transcript levels drop. Single-cell RNA cytometry analysis revealed a bi-modal distributed Birc6 mRNA expression heterogeneity within mouse hematopoietic stem cell (HSC) population. Upon ageing, BIRC6-high expressing HSC cells were shown to out-compete Birc6-low cells (Dimov et al., 2014). BIRC6 is frequently elevated in various cancer tissues.
Localisation Localized to membranes of the trans Golgi network (TGN) and the endosomal system (Hauser et al., 1998). BIRC6 relocalizes considerably during the cell cycle. It concentrates in a pericentriolar compartment in interphase, moves partially to spindle poles in metaphase, and finally localizes to the spindle midzone and the midbody in telophase and during cytokinesis (Pohl and Jentsch, 2008).
Function Inhibitor of apoptosis. BIRC6 is a peripheral membrane protein of the trans-Golgi network that protects cells from apoptosis by functioning as an inhibitor of apoptosis protein (IAP). BIRC6 can bind and inhibit activated caspases CASP-3, CASP-6, CASP-7, CASP-8 and CASP-9. Furthermore it ubiquitylates caspase-9, HtrA2 (a pro-apoptotic serine protease) and DIABLO/Smac (a competitor for caspase-IAP interactions) thereby targeting them for proteasomal degradation. The ubiquityltion reactions do not require an ubiquitin E3 ligase making BIRC6 a chimeric E2/E3 ubiquitin ligase (Bartke et al., 2004; Hao et al., 2004). More importantly, distinct from other IAP members, BIRC6 is able to antagonize both precursor and mature forms of Smac and caspase-9. The ability to antagonize precursor apoptotic molecules represents an important mechanism for the prevention of apoptosis under normal conditions (Qiu and Goldberg, 2005). On the other hand, BIRC6 also inhibits apoptosis via negatively regulating p53 protein levels by facilitating its degradation via ubiquitination (Ren et al., 2005; Tang et al., 2014).
BIRC6 and treatment resistance. Silencing of BIRC6 has been shown to sensitize cancer cells to various anticancer agents, including 5-fluorouracil (in cervical, fibrosarcoma and breast cancer cells) (Chu et al., 2008), oxaliplatin and cisplatin (in colonospheres) (Van Houdt et al., 2011), MEK inhibitor, BRAFV600E-specific inhibitor and soluble or membrane-bound TRAIL (in melanoma cells) (Tassi et al., 2012), cisplatin (in non-small cell lung cancer and glioma) (Dong et al., 2013; Chen et al., 1999), camptothecin (glioma) (Chen et al., 1999) and sorafenib (in hepatoma) (Tang et al., 2014).
Essential in embryonic development. Targeted disruption of BIRC6 in mice caused embryonic and neonatal lethality. BIRC6 homozygous-mutant embryos which did not express BIRC6 all died immediately after birth. At E18.5, viable mutant embryos had normal appearance, but were significantly smaller (10-20% less body weight) than control littermates. Macroscopic analysis of mutant embryos at E15.5 revealed that more than half of them had severely defective angiogenesis that often coincided with severe oedema (Hao et al., 2004). Consistantly, BIRC6 knock-out mice showed retarded growth and poor vascularization from E13.5 and perinatal lethality (Lotz et al., 2004). BIRC6 mutant mice were embryonic lethal (Hitz et al., 2000; Ren et al., 2005).
Regulator of cytokinesis. BIRC6 is a major regulator of abscission, the final stage of cytokinesis. During cytokinesis, BIRC6 moves from the vesicular system to the midbody ring and serves as a platform for the membrane delivery machinery and mitotic regulators. Depletion of BIRC6 in cell cultures causes defective abscission and cytokinesis-associated apoptosis, accompanied by a block of vesicular targeting and defective formation of the midbody and the midbody ring. BIRC6 coordinates multiple steps required for abscission including the relocalization of ubiquitin from midbody microtubules to the midbody ring during cytokinesis (Pohl and Jentsch, 2008).
Novel regulator of mitosis. BIRC6 interacts with cyclin A and promotes its degradation in early mitosis. BIRC6 also interacts with APC/C, and it facilitates cyclin A ubiquitylation. The elimination of cyclin A and cyclin B are essential for entry into mitosis. BIRC6 -deficient MEF cells exhibit earlier replicative senescence, large nuclei with excess centrosome, and mitotic delay. BIRC6 facilitates the ubiquitylation of CYCLIN A by recruiting it to APC/C without the need of a functional UBC domain, suggesting its role as a substrate recognition subunit in a complex of ubiquitin ligase (Kikuchi et al., 2014).
BIRC6 and autophagy. Functional BIRC6 is required to inhibit autophagy under nutrient-rich conditions in D. melanogaster oogenesis. Lack of BIRC6 function in BIR-domain deleted flies resulted in an increase in both autophagic punctate and TUNEL staining in germaria and degenerating midstage egg chambers (Hou et al., 2008). On the contrary, recent evidence suggested that BIRC6 may promote autophagy in prostate cancer cells. Silencing of BIRC6 was showed to decrease Beclin-1 protein, LC3 cleavage and reduce LC3 punctate formation (Low et al., 2013).

Regulation of BIRC6
Despite the ability of BIRC6 to target caspases, Smac and HtrA2, BIRC6 is also negatively regulated by these pro-apoptotic molecules. Caspase-3 and HtrA2 are capable of cleaving BIRC6 and inhibit its anti-apoptotic function. Smac inhibits the IAP function of BIRC6 by its ability to block BIRC6-caspase binding (Bartke et al., 2004; Sekine et al., 2005). Nrdp1, a RING finger containing ubiquitin ligase, promotes proteasomal degradation of BIRC6 (Qiu et al., 2004).
Epstein-Barr Virus (EBV) microRNAs (miRNAs) processed from the BHRF1 and BamHI A rightward (BART) transcript, miR-BART15-3p, targets the 3' untranslated region (UTR) of BIRC6. miR-BART15-3p inhibits the translation of BIRC6 protein in EBV-infected gastric carcinoma cells and contributes to host cells apoptosis induction (Choi et al., 2013). In muscle, prostaglandin F2a upregulates BIRC6 which promotes muscle cell survival and growth (Jansen and Pavlath, 2008).

 
  Summary of the pleiotropic functions of BIRC6.
Homology - ubc-17 (C. elegans)
- IAP6 (A. gambiae)
- Bruce (D. melanogaster)
- BIRC6 (X. tropicalis)
- Birc6 (M. musculus)

Mutations

Note There are several synonymous and nonsynonymous SNPs reported for BIRC6 (E589K, L1742F, R2187T, T2646S, T3708N, E3864K, Q4323H, N4324Y, S4325C, N4326T, P4329R).

Implicated in

Entity Myelodysplastic syndromes
Note Bone marrow cells of myelodysplastic syndromes exhibit significant expression of BIRC6 (Abe et al., 2005).
  
Entity Childhood acute myeloid leukemia
Prognosis BIRC6 elevation associated with poor prognosis in childhood de novo Acute Myeloid Leukemia: BIRC6 overexpression (>median expression) was associated with an unfavorable day 7 response to induction chemotherapy and also associated with a poorer 3-year relapse-free survival rate (Sung et al., 2007).
  
Entity Acute myeloid leukemia
Note BIRC6 mRNA expression was associated with the differentiation status of AML cells.
BIRC6 mRNA expression was induced upon neutrophil differentiation of AML cells, whereas knocking-down BIRC6 attenuates neutrophil differentiation of APL cells without altering cell survival.
Cytogenetics AML patient samples with the t(8;21), the t(15;17) or a complex karyotype express BIRC6 significantly lower than normal human granulocytes (Schläfli et al., 2012).
  
Entity Colorectal cancer
Note BIRC6 expression increased in colorectal cancer tissue and stem-like cells enriched colonosphere.
BIRC6 mRNA expression was significantly up-regulated in primary colorectal cancer tissues compared with normal mucosa (Bianchini et al., 2006). Moreover, BIRC6 protein highly up-regulated in patient derived colonosphere compared with differentiated counterpart. Knockdown of BIRC6 sensitized colonosphere against the chemotherapeutic drugs oxaliplatin and cisplatin in vitro. (Van Houdt et al, 2011).
  
Entity Brain cancers
Note Elevated expression in brain cancers.
BIRC6 knockdown induces apoptosis in neuroblastoma cells and associated with increased DIABLO protein expression in cytoplasm (Lamers et al., 2012). It is also overexpressed in glioma cell lines (SF-268, SNB-78) (Chen et al., 1999).
Cytogenetics Frequent gain of the BIRC6 gene on chromosome 2 neuroblastoma tumors, which resulted in increased BIRC6 mRNA expression (Lamers et al., 2012).
  
Entity Melanoma
Note BIRC6 is constitutively expressed in melanoma and promote resistance to antitumor agents.
BIRC6 was constitutively expressed by melanoma cells, in vitro and in patient samples, and at higher levels than in benign melanocytic lesions. Melanoma susceptibility to apoptosis by cytotoxic drugs fotemustine and target-specific inhibitors (MEK inhibitor and BRAFV600E-specific inhibitor) correlated with down-modulation of BIRC6 protein. The antitumor agents promoted BIRC6 downmodulation, is caspase independent and proteasome dependent. Moreover, targeting of BIRC6, by siRNA, significantly enhanced caspase-dependent melanoma apoptosis in response to cytotoxic drugs, MEK, and BRAFV600E inhibitors and soluble or membrane-bound TRAIL (Tassi et al., 2012).
  
Entity Non-small cell lung cancer (NSCLC)
Note Elevated expression in non-small cell lung cancer (NSCLC).
BIRC6 down-regulation inhibited growth of the NSCLC cells and sensitized the cells to cisplatin in vitro.
Prognosis Elevated BIRC6 protein expression in NSCLC tissues was associated with poor 3-year relapse-free patient survival, regional lymph node metastasis, and advanced pathological tumor, node, metastasis stage. (Dong et al., 2013).
  
Entity Prostate cancer
Note BIRC6 is elevated in advanced prostate cancer and important in promoting growth and suppressing apoptosis.
Elevated BIRC6 protein expression was found in prostate cancer cell lines and clinical specimens compared to benign tissue. In particular, increased BIRC6 expression was associated with Gleason 6-8 cancers, castration resistance, higher clinical T stages and correlates with the presence of poor prognostic factors including PSA recurrence, lymph node metastasis and prostatic capsule invasion (Low et al., 2013; Luk et al., 2014).
  
Entity Epithelial ovarian cancer
Note Elevated expression and poor prognostic factor in epithelial ovarian cancer.
BIRC6 expression was higher in the epithelial ovarian cancer (EOC) tissue than in normal control tissue at protein level.
Prognosis BIRC6 was an independent significant predictor for overall survival and disease-free survival. Cytoplasmic BIRC6 expression is associated with EOC differentiation (Wang et al., 2014).
  
Entity Hepatocellular carcinoma (HCC)
Note BIRC6 promotes hepatocellular carcinogenesis and associates with poor patient survival and prognosis.
BIRC6 knockdown suppressed hepatoma cell proliferation, caused G1/S arrest and sensitized hepatoma cells to sorafenib-induced apoptosis in vitro and in vivo.
Prognosis BIRC6 overexpression was significantly correlated with serum alanine aminotransferase level and HCC vascular invasion in patient samples. Patients with BIRC6 positive expression in tumor tissue had a poor survival and a high rate of recurrence (Tang et al., 2014).
  
Entity Breast cancer
Note BIRC6 promotes cell growth and inhibiting apoptosis in breast cancer cells with wild type p53.
BIRC6 knockdown resulted in a marked decline of cell growth and an increased rate of apoptosis in wild-type p53 ZR75.1 cells, which was associated with p53 stabilisation and activation of the mitochondrial-dependent apoptotic pathway. A less pronounced anti-proliferative and pro-apoptotic effects were observed in mutant p53 breast cancer cells (Lopergolo et al., 2009).
  
Entity Pseudoexfoliative glaucoma (PEXG)
Note Polymorphism in the BIRC6 Gene plays a protective role in Pseudoexfoliative Glaucoma.
Prognosis TT allele of the rs2754511 in the BIRC6 gene plays a protective role in PEXG patients of the Pakistani population (Ayub et al., 2014).
  

External links

Nomenclature
HGNC (Hugo)BIRC6   13516
Cards
AtlasBIRC6ID798ch2p22
Entrez_Gene (NCBI)BIRC6  57448  baculoviral IAP repeat containing 6
GeneCards (Weizmann)BIRC6
Ensembl hg19 (Hinxton)ENSG00000115760 [Gene_View]  chr2:32582096-32843965 [Contig_View]  BIRC6 [Vega]
Ensembl hg38 (Hinxton)ENSG00000115760 [Gene_View]  chr2:32582096-32843965 [Contig_View]  BIRC6 [Vega]
ICGC DataPortalENSG00000115760
cBioPortalBIRC6
AceView (NCBI)BIRC6
Genatlas (Paris)BIRC6
WikiGenes57448
SOURCE (Princeton)BIRC6
Genomic and cartography
GoldenPath hg19 (UCSC)BIRC6  -     chr2:32582096-32843965 +  2p22.3   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)BIRC6  -     2p22.3   [Description]    (hg38-Dec_2013)
EnsemblBIRC6 - 2p22.3 [CytoView hg19]  BIRC6 - 2p22.3 [CytoView hg38]
Mapping of homologs : NCBIBIRC6 [Mapview hg19]  BIRC6 [Mapview hg38]
OMIM605638   
Gene and transcription
Genbank (Entrez)AA315620 AB033115 AF265555 AK023788 AK023848
RefSeq transcript (Entrez)NM_016252
RefSeq genomic (Entrez)AC_000134 NC_000002 NC_018913 NT_022184 NW_001838769 NW_004929300
Consensus coding sequences : CCDS (NCBI)BIRC6
Cluster EST : UnigeneHs.150107 [ NCBI ]
CGAP (NCI)Hs.150107
Alternative Splicing : Fast-db (Paris)GSHG0016362
Alternative Splicing GalleryENSG00000115760
Gene ExpressionBIRC6 [ NCBI-GEO ]     BIRC6 [ SEEK ]   BIRC6 [ MEM ]
SOURCE (Princeton)Expression in : [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9NR09 (Uniprot)
NextProtQ9NR09  [Medical]
With graphics : InterProQ9NR09
Splice isoforms : SwissVarQ9NR09 (Swissvar)
Catalytic activity : Enzyme6.3.2.- [ Enzyme-Expasy ]   6.3.2.-6.3.2.- [ IntEnz-EBI ]   6.3.2.- [ BRENDA ]   6.3.2.- [ KEGG ]   
Domaine pattern : Prosite (Expaxy)BIR_REPEAT_2 (PS50143)    UBIQUITIN_CONJUGAT_2 (PS50127)   
Domains : Interpro (EBI)BIR    BIRC6    UBQ-conjugat_E2    UBQ-conjugating_enzyme/RWD    WD40/YVTN_repeat-like_dom   
Related proteins : CluSTrQ9NR09
Domain families : Pfam (Sanger)BIR (PF00653)    DUF3643 (PF12356)    UQ_con (PF00179)   
Domain families : Pfam (NCBI)pfam00653    pfam12356    pfam00179   
Domain families : Smart (EMBL)BIR (SM00238)  
DMDM Disease mutations57448
Blocks (Seattle)Q9NR09
PDB (SRS)3CEG   
PDB (PDBSum)3CEG   
PDB (IMB)3CEG   
PDB (RSDB)3CEG   
Human Protein AtlasENSG00000115760
Peptide AtlasQ9NR09
HPRD05731
IPIIPI00939720   IPI00893564   IPI00893758   
Protein Interaction databases
DIP (DOE-UCLA)Q9NR09
IntAct (EBI)Q9NR09
FunCoupENSG00000115760
BioGRIDBIRC6
IntegromeDBBIRC6
STRING (EMBL)BIRC6
Ontologies - Pathways
QuickGOQ9NR09
Ontology : AmiGOspindle pole  ubiquitin-protein transferase activity  cysteine-type endopeptidase inhibitor activity  protein binding  endosome  trans-Golgi network  microtubule organizing center  protein phosphorylation  apoptotic process  mitotic nuclear division  positive regulation of cell proliferation  negative regulation of endopeptidase activity  negative regulation of endopeptidase activity  membrane  protein ubiquitination  acid-amino acid ligase activity  midbody  regulation of cytokinesis  regulation of cell proliferation  negative regulation of apoptotic process  negative regulation of apoptotic process  labyrinthine layer development  spongiotrophoblast layer development  negative regulation of extrinsic apoptotic signaling pathway  
Ontology : EGO-EBIspindle pole  ubiquitin-protein transferase activity  cysteine-type endopeptidase inhibitor activity  protein binding  endosome  trans-Golgi network  microtubule organizing center  protein phosphorylation  apoptotic process  mitotic nuclear division  positive regulation of cell proliferation  negative regulation of endopeptidase activity  negative regulation of endopeptidase activity  membrane  protein ubiquitination  acid-amino acid ligase activity  midbody  regulation of cytokinesis  regulation of cell proliferation  negative regulation of apoptotic process  negative regulation of apoptotic process  labyrinthine layer development  spongiotrophoblast layer development  negative regulation of extrinsic apoptotic signaling pathway  
Pathways : KEGGUbiquitin mediated proteolysis   
Protein Interaction DatabaseBIRC6
DoCM (Curated mutations)BIRC6
Wikipedia pathwaysBIRC6
Gene fusion - rearrangements
Polymorphisms : SNP, variants
NCBI Variation ViewerBIRC6 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)BIRC6
dbVarBIRC6
ClinVarBIRC6
1000_GenomesBIRC6 
Exome Variant ServerBIRC6
SNP (GeneSNP Utah)BIRC6
SNP : HGBaseBIRC6
Genetic variants : HAPMAPBIRC6
Genomic VariantsBIRC6  BIRC6 [DGVbeta]
Mutations
ICGC Data PortalENSG00000115760 
Somatic Mutations in Cancer : COSMICBIRC6 
CONAN: Copy Number AnalysisBIRC6 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)2:32582096-32843965
Mutations and Diseases : HGMDBIRC6
OMIM605638   
MedgenBIRC6
NextProtQ9NR09 [Medical]
GENETestsBIRC6
Disease Genetic AssociationBIRC6
Huge Navigator BIRC6 [HugePedia]  BIRC6 [HugeCancerGEM]
snp3D : Map Gene to Disease57448
DGIdb (Drug Gene Interaction db)BIRC6
General knowledge
Homologs : HomoloGeneBIRC6
Homology/Alignments : Family Browser (UCSC)BIRC6
Phylogenetic Trees/Animal Genes : TreeFamBIRC6
Chemical/Protein Interactions : CTD57448
Chemical/Pharm GKB GenePA25363
Clinical trialBIRC6
Cancer Resource (Charite)ENSG00000115760
Other databases
Probes
Litterature
PubMed45 Pubmed reference(s) in Entrez
CoreMineBIRC6
GoPubMedBIRC6
iHOPBIRC6

Bibliography

A giant ubiquitin-conjugating enzyme related to IAP apoptosis inhibitors.
Hauser HP, Bardroff M, Pyrowolakis G, Jentsch S.
J Cell Biol. 1998 Jun 15;141(6):1415-22.
PMID 9628897
 
A human IAP-family gene, apollon, expressed in human brain cancer cells.
Chen Z, Naito M, Hori S, Mashima T, Yamori T, Tsuruo T.
Biochem Biophys Res Commun. 1999 Nov 2;264(3):847-54.
PMID 10544019
 
Inhibitor of apoptosis proteins and their relatives: IAPs and other BIRPs.
Verhagen AM, Coulson EJ, Vaux DL.
Genome Biol. 2001;2(7):REVIEWS3009. Epub 2001 Jul 5. (REVIEW)
PMID 11516343
 
Drosophila Bruce can potently suppress Rpr- and Grim-dependent but not Hid-dependent cell death.
Vernooy SY, Chow V, Su J, Verbrugghe K, Yang J, Cole S, Olson MR, Hay BA.
Curr Biol. 2002 Jul 9;12(13):1164-8.
PMID 12121627
 
Dual role of BRUCE as an antiapoptotic IAP and a chimeric E2/E3 ubiquitin ligase.
Bartke T, Pohl C, Pyrowolakis G, Jentsch S.
Mol Cell. 2004 Jun 18;14(6):801-11.
PMID 15200957
 
Apollon ubiquitinates SMAC and caspase-9, and has an essential cytoprotection function.
Hao Y, Sekine K, Kawabata A, Nakamura H, Ishioka T, Ohata H, Katayama R, Hashimoto C, Zhang X, Noda T, Tsuruo T, Naito M.
Nat Cell Biol. 2004 Sep;6(9):849-60. Epub 2004 Aug 8.
PMID 15300255
 
BRUCE, a giant E2/E3 ubiquitin ligase and inhibitor of apoptosis protein of the trans-Golgi network, is required for normal placenta development and mouse survival.
Lotz K, Pyrowolakis G, Jentsch S.
Mol Cell Biol. 2004 Nov;24(21):9339-50.
PMID 15485903
 
An Apollon vista of death and destruction.
Martin SJ.
Nat Cell Biol. 2004 Sep;6(9):804-6.
PMID 15340445
 
Nrdp1-mediated degradation of the gigantic IAP, BRUCE, is a novel pathway for triggering apoptosis.
Qiu XB, Markant SL, Yuan J, Goldberg AL.
EMBO J. 2004 Feb 25;23(4):800-10. Epub 2004 Feb 12.
PMID 14765125
 
Bone marrow cells of myelodysplastic syndromes exhibit significant expression of apollon, livin and ILP-2 with reduction after transformation to overt leukemia.
Abe S, Yamamoto K, Hasegawa M, Inoue M, Kurata M, Hirokawa K, Kitagawa M, Nakagawa Y, Suzuki K.
Leuk Res. 2005 Sep;29(9):1095-6. Epub 2005 Mar 16.
PMID 16038738
 
Progressive loss of the spongiotrophoblast layer of Birc6/Bruce mutants results in embryonic lethality.
Hitz C, Vogt-Weisenhorn D, Ruiz P, Wurst W, Floss T.
Genesis. 2005 Jun;42(2):91-103.
PMID 15887267
 
The membrane-associated inhibitor of apoptosis protein, BRUCE/Apollon, antagonizes both the precursor and mature forms of Smac and caspase-9.
Qiu XB, Goldberg AL.
J Biol Chem. 2005 Jan 7;280(1):174-82. Epub 2004 Oct 26.
PMID 15507451
 
The Birc6 (Bruce) gene regulates p53 and the mitochondrial pathway of apoptosis and is essential for mouse embryonic development.
Ren J, Shi M, Liu R, Yang QH, Johnson T, Skarnes WC, Du C.
Proc Natl Acad Sci U S A. 2005 Jan 18;102(3):565-70. Epub 2005 Jan 7.
PMID 15640352
 
HtrA2 cleaves Apollon and induces cell death by IAP-binding motif in Apollon-deficient cells.
Sekine K, Hao Y, Suzuki Y, Takahashi R, Tsuruo T, Naito M.
Biochem Biophys Res Commun. 2005 Apr 29;330(1):279-85.
PMID 15781261
 
Bruce/apollon promotes hippocampal neuron survival and is downregulated by kainic acid.
Sokka AL, Mudo G, Aaltonen J, Belluardo N, Lindholm D, Korhonen L.
Biochem Biophys Res Commun. 2005 Dec 16;338(2):729-35. Epub 2005 Oct 11.
PMID 16236253
 
Comparative study of gene expression by cDNA microarray in human colorectal cancer tissues and normal mucosa.
Bianchini M, Levy E, Zucchini C, Pinski V, Macagno C, De Sanctis P, Valvassori L, Carinci P, Mordoh J.
Int J Oncol. 2006 Jul;29(1):83-94.
PMID 16773188
 
Overexpression of Apollon, an antiapoptotic protein, is associated with poor prognosis in childhood de novo acute myeloid leukemia.
Sung KW, Choi J, Hwang YK, Lee SJ, Kim HJ, Lee SH, Yoo KH, Jung HL, Koo HH.
Clin Cancer Res. 2007 Sep 1;13(17):5109-14.
PMID 17785565
 
Oncolytic adenovirus-mediated shRNA against Apollon inhibits tumor cell growth and enhances antitumor effect of 5-fluorouracil.
Chu L, Gu J, Sun L, Qian Q, Qian C, Liu X.
Gene Ther. 2008 Apr;15(7):484-94. doi: 10.1038/gt.2008.6. Epub 2008 Jan 31.
PMID 18239605
 
Effector caspase Dcp-1 and IAP protein Bruce regulate starvation-induced autophagy during Drosophila melanogaster oogenesis.
Hou YC, Chittaranjan S, Barbosa SG, McCall K, Gorski SM.
J Cell Biol. 2008 Sep 22;182(6):1127-39. doi: 10.1083/jcb.200712091. Epub 2008 Sep 15.
PMID 18794330
 
Prostaglandin F2alpha promotes muscle cell survival and growth through upregulation of the inhibitor of apoptosis protein BRUCE.
Jansen KM, Pavlath GK.
Cell Death Differ. 2008 Oct;15(10):1619-28. doi: 10.1038/cdd.2008.90. Epub 2008 Jun 20.
PMID 18566603
 
Final stages of cytokinesis and midbody ring formation are controlled by BRUCE.
Pohl C, Jentsch S.
Cell. 2008 Mar 7;132(5):832-45. doi: 10.1016/j.cell.2008.01.012.
PMID 18329369
 
Apollon gene silencing induces apoptosis in breast cancer cells through p53 stabilisation and caspase-3 activation.
Lopergolo A, Pennati M, Gandellini P, Orlotti NI, Poma P, Daidone MG, Folini M, Zaffaroni N.
Br J Cancer. 2009 Mar 10;100(5):739-46. doi: 10.1038/sj.bjc.6604927. Epub 2009 Feb 17.
PMID 19223905
 
Comparative proteomics of colon cancer stem cells and differentiated tumor cells identifies BIRC6 as a potential therapeutic target.
Van Houdt WJ, Emmink BL, Pham TV, Piersma SR, Verheem A, Vries RG, Fratantoni SA, Pronk A, Clevers H, Borel Rinkes IH, Jimenez CR, Kranenburg O.
Mol Cell Proteomics. 2011 Dec;10(12):M111.011353. doi: 10.1074/mcp.M111.011353. Epub 2011 Jul 25.
PMID 21788403
 
Identification of BIRC6 as a novel intervention target for neuroblastoma therapy.
Lamers F, Schild L, Koster J, Speleman F, Ora I, Westerhout EM, van Sluis P, Versteeg R, Caron HN, Molenaar JJ.
BMC Cancer. 2012 Jul 12;12:285. doi: 10.1186/1471-2407-12-285.
PMID 22788920
 
BIRC6 (APOLLON) is down-regulated in acute myeloid leukemia and its knockdown attenuates neutrophil differentiation.
Schlafli AM, Torbett BE, Fey MF, Tschan MP.
Exp Hematol Oncol. 2012 Sep 4;1(1):25. doi: 10.1186/2162-3619-1-25.
PMID 23211188
 
Role of Apollon in human melanoma resistance to antitumor agents that activate the intrinsic or the extrinsic apoptosis pathways.
Tassi E, Zanon M, Vegetti C, Molla A, Bersani I, Perotti V, Pennati M, Zaffaroni N, Milella M, Ferrone S, Carlo-Stella C, Gianni AM, Mortarini R, Anichini A.
Clin Cancer Res. 2012 Jun 15;18(12):3316-27. doi: 10.1158/1078-0432.CCR-11-2232. Epub 2012 May 2.
PMID 22553342
 
Epstein-Barr virus-encoded microRNA BART15-3p promotes cell apoptosis partially by targeting BRUCE.
Choi H, Lee H, Kim SR, Gho YS, Lee SK.
J Virol. 2013 Jul;87(14):8135-44. doi: 10.1128/JVI.03159-12. Epub 2013 May 15.
PMID 23678170
 
Elevated expression of BIRC6 protein in non-small-cell lung cancers is associated with cancer recurrence and chemoresistance.
Dong X, Lin D, Low C, Vucic EA, English JC, Yee J, Murray N, Lam WL, Ling V, Lam S, Gout PW, Wang Y.
J Thorac Oncol. 2013 Feb;8(2):161-70. doi: 10.1097/JTO.0b013e31827d5237.
PMID 23287853
 
BIRC6 protein, an inhibitor of apoptosis: role in survival of human prostate cancer cells.
Low CG, Luk IS, Lin D, Fazli L, Yang K, Xu Y, Gleave M, Gout PW, Wang Y.
PLoS One. 2013;8(2):e55837. doi: 10.1371/journal.pone.0055837. Epub 2013 Feb 8.
PMID 23409057
 
Association of a polymorphism in the BIRC6 gene with pseudoexfoliative glaucoma.
Ayub H, Micheal S, Akhtar F, Khan MI, Bashir S, Waheed NK, Ali M, Schoenmaker-Koller FE, Shafique S, Qamar R, Hollander AI.
LoS One. 2014 Aug 13;9(8):e105023. doi: 10.1371/journal.pone.0105023. eCollection 2014.
PMID 25118708
 
Discriminating cellular heterogeneity using microwell-based RNA cytometry.
Dimov IK, Lu R, Lee EP, Seita J, Sahoo D, Park SM, Weissman IL, Lee LP.
Nat Commun. 2014 Mar 25;5:3451. doi: 10.1038/ncomms4451.
PMID 24667995
 
APOLLON protein promotes early mitotic CYCLIN A degradation independent of the spindle assembly checkpoint.
Kikuchi R, Ohata H, Ohoka N, Kawabata A, Naito M.
J Biol Chem. 2014 Feb 7;289(6):3457-67. doi: 10.1074/jbc.M113.514430. Epub 2013 Dec 3.
PMID 24302728
 
The BIRC6 gene as a novel target for therapy of prostate cancer: dual targeting of inhibitors of apoptosis.
Luk SU, Xue H, Cheng H, Lin D, Gout PW, Fazli L, Collins CC, Gleave ME, Wang Y.
Oncotarget. 2014 Aug 30;5(16):6896-908.
PMID 25071009
 
BIRC6 promotes hepatocellular carcinogenesis: Interaction of BIRC6 with p53 facilitating p53 degradation.
Tang W, Xue R, Weng S, Wu J, Fang Y, Wang Y, Ji L, Hu T, Liu T, Huang X, Chen S, Shen X, Zhang S, Dong L.
Int J Cancer. 2014 Sep 6. doi: 10.1002/ijc.29194. [Epub ahead of print]
PMID 25196217
 
Expression and clinical significance of BIRC6 in human epithelial ovarian cancer.
Wang L, Chen YJ, Hou J, Wang YY, Tang WQ, Shen XZ, Tu RQ.
Tumour Biol. 2014 May;35(5):4891-6. doi: 10.1007/s13277-014-1641-6. Epub 2014 Jan 23.
PMID 24453032
 
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Contributor(s)

Written11-2006Christian Pohl, Stefan Jentsch
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Updated10-2014Sze Ue Iris Luk, Yuzhuo Wang
The Vancouver Prostate Centre, Vancouver General Hospital and Department of Urologic Sciences, the University of British Columbia, Vancouver, BC, Canada (SUIL, YW); Department of Experimental Therapeutics, BC Cancer Agency, Vancouver, BC, Canada (SUIL, YW)

Citation

This paper should be referenced as such :
Iris Luk SU, Wang Y
BIRC6 (Baculoviral IAP repeat-containing 6);
Atlas Genet Cytogenet Oncol Haematol. October 2014
Free online version   Free pdf version   [Bibliographic record ]
Atlas Genet Cytogenet Oncol Haematol. October 2014
URL : http://AtlasGeneticsOncology.org/Genes/BIRC6ID798ch2p22.html

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