| Written | 2008-01 | Stéphanie Plenchette, Wai Gin Fong, Robert G Korneluk |
| Children's Hospital of Eastern Ontario, Apoptosis Research Centre, Research Institute, 401 Smyth Road, Ottawa, ON, K1H 8L1, Canada |
| Identity |
| Alias_symbol (synonym) | BIRC4BP |
| XIAPAF1 | |
| HSXIAPAF1 | |
| Other alias | |
| HGNC (Hugo) | XAF1 |
| LocusID (NCBI) | 54739 |
| Atlas_Id | 44095 |
| Location | 17p13.1 [Link to chromosome band 17p13] |
| Location_base_pair | Starts at 6755837 and ends at 6775645 bp from pter ( according to hg19-Feb_2009) [Mapping XAF1.png] |
| Local_order | Telomeric to TP53 gene (17p13.1) |
| Fusion genes (updated 2016) | XAF1 (17p13.1) / FAM64A (17p13.2) | XAF1 (17p13.1) / SLC8A1 (2p22.1) |
| DNA/RNA |
 | |
| Schematic diagram of the XAF1 gene comprising 8 exons (in grey) and transcript variants. The sizes in base pairs (bp) of exons (above) and introns (below) are shown. (*) indicates the positions of the stop codons. | |
| Description | The XAF1 gene exists as a single copy in the human genome; it contains 8 exons and was predicted to span over approximately 18 kb of the genomic DNA. |
| Transcription | Five isoforms of XAF1 cDNA have been identified and are expressed in a cell and tissue type specific-manner: The original XAF1, also called XAF1(A) (CDS: 906nt) The XAF1(B) isoform (CDS: 849nt); lacks exon 3 The XAF1(C) isoform (CDS: 495nt); contains exon 4b and a new stop codon The XAF1(D) isoform (CDS: 426nt); lacks exons 4b and 5 (new stop codon in exon 6) The XAF1(E) isoform (CDS: 369nt); lacks exons 3, 4b and 5 (new stop codon in exon 6) With Northern blot analysis, at least four distinct transcripts sizes have been identified in Homo sapiens (3.9 kb, 4.5 kb, 6.0 kb and 7.0 kb). How these mRNA species relate to isoform variants is not known. |
| Pseudogene | Not known |
| Protein |
| Description | The full length XAF1 protein consists of 301 amino acids corresponding to a molecular weight of 33.411 kDa. The protein contains seven zinc fingers domains. The XAF1(B) isoform is predicted to lack the third N-terminal zinc finger of the previously described XAF1. The XAF1(C) is predicted to contain the first five amino-terminal zinc finger domains of the previously described XAF1 and also a unique 24 aa carboxy terminus. There is no evidence for XAF1 isoforms (C), (D) and (E) expression at the protein level. |
| Expression | Normal tissue: ubiquitous and differential expression in normal tissues; highest in heart and ovary and lowest in brain and testis at mRNA levels. The XAF1 protein also displays differential protein expression profile within normal cell or tissue development including placenta and motoneurons. Cancer: as opposed to normal cells, XAF1 is found either low or undetectable in tumor cell lines at both mRNA and protein levels. Expression varies also widely among different tumor cell lines. High levels of XAF1 protein were found in glioblastoma cells (SF-539) and ovarian cells (OVCAR-5). Detectable levels were found also in various gastric and colon cancer cell lines and also myeloma cells (U266). |
| Localisation | Nuclear and cytoplasmic distribution |
| Function | Tumor suppressor gene: loss of heterozygosity (LOH) found in 12 of 33 (36%) human primary colorectal carcinomas. The absence or reduced expression of XAF1 in cancer cell lines by genetic or epigenetic modifications have suggested a possible role in the suppression of development and/or progression of malignancy. IAP antagonist: XAF1 exerts a proapoptotic effect by directly interacting with BIRC4/XIAP and antagonizing its anticaspase activity. XAF1 enhances XIAP E3 ligase activity towards BIRC5/Survivin through a complex and mediates Survivin down-regulation. Interferon (IFN)-stimulated gene (ISG): XAF1 is an important mediator of IFN-induced sensitization to TNF-related apoptosis-inducing ligand (TRAIL) in cancer. Increasing expression of XAF1 sensitizes cells to apoptosis-induced by various stimuli including etoposide, 5-FU, TRAIL, anti-Fas Ab, TNFalpha, UV, H2O2, gamma-irradiation. |
| Homology | XAF1 shares high amino acid similarity with the zinc finger domains of FLN29 and TRAF6. |
| Mutations |
| Note | Include genetic and epigenetic modification |
| Epigenetics | Aberrant promoter hypermethylation in the 5' proximal region (from +3nt to -234 nt) in a variety of gastric, colon, bladder, kidney and prostate cancer cell lines and tumors. |
| Germinal | Not known |
| Somatic | No somatic mutations in tumor cell lines examined. LOH described in colon tumors. |
| Implicated in |
| Note | |
| Entity | Colorectal cancer, gastric cancer, urogenital cancer |
| Oncogenesis | XAF1 is proposed to be a tumor suppressor gene. Correlation of reduction in XAF1 expression with stage and grade within gastric and colorectal tumors demonstrating that the loss of XAF1 contributes to tumorigenesis. |
| Bibliography |
| Degradation of survivin by the X-linked inhibitor of apoptosis (XIAP)-XAF1 complex. |
| Arora V, Cheung HH, Plenchette S, Micali OC, Liston P, Korneluk RG |
| The Journal of biological chemistry. 2007 ; 282 (36) : 26202-26209. |
| PMID 17613533 |
| Hypermethylation of XIAP-associated factor 1, a putative tumor suppressor gene from the 17p13.2 locus, in human gastric adenocarcinomas. |
| Byun DS, Cho K, Ryu BK, Lee MG, Kang MJ, Kim HR, Chi SG |
| Cancer research. 2003 ; 63 (21) : 7068-7075. |
| PMID 14612497 |
| Frequent alteration of XAF1 in human colorectal cancers: implication for tumor cell resistance to apoptotic stresses. |
| Chung SK, Lee MG, Ryu BK, Lee JH, Han J, Byun DS, Chae KS, Lee KY, Jang JY, Kim HJ, Chi SG |
| Gastroenterology. 2007 ; 132 (7) : 2459-2477. |
| PMID 17570219 |
| Switch to full-length of XAF1 mRNA expression in prostate cancer cells by the DNA methylation inhibitor. |
| Fang X, Liu Z, Fan Y, Zheng C, Nilson S, Egevad L, Ekman P, Xu D |
| International journal of cancer. Journal international du cancer. 2006 ; 118 (10) : 2485-2489. |
| PMID 16353137 |
| Expression and genetic analysis of XIAP-associated factor 1 (XAF1) in cancer cell lines. |
| Fong WG, Liston P, Rajcan-Separovic E, St Jean M, Craig C, Korneluk RG |
| Genomics. 2000 ; 70 (1) : 113-122. |
| PMID 11087668 |
| Gene expression and promoter methylation of the XIAP-associated Factor 1 in renal cell carcinomas: correlations with pathology and outcome. |
| Kempkensteffen C, Hinz S, Schrader M, Christoph F, Magheli A, Krause H, Schostak M, Miller K, Weikert S |
| Cancer letters. 2007 ; 254 (2) : 227-235. |
| PMID 17449173 |
| Identification of X-linked inhibitor of apoptosis-associated factor-1 as an interferon-stimulated gene that augments TRAIL Apo2L-induced apoptosis. |
| Leaman DW, Chawla-Sarkar M, Vyas K, Reheman M, Tamai K, Toji S, Borden EC |
| The Journal of biological chemistry. 2002 ; 277 (32) : 28504-28511. |
| PMID 12029096 |
| Promoter CpG hypermethylation and downregulation of XAF1 expression in human urogenital malignancies: implication for attenuated p53 response to apoptotic stresses. |
| Lee MG, Huh JS, Chung SK, Lee JH, Byun DS, Ryu BK, Kang MJ, Chae KS, Lee SJ, Lee CH, Kim JI, Chang SG, Chi SG |
| Oncogene. 2006 ; 25 (42) : 5807-5822. |
| PMID 16909101 |
| Identification of XAF1 as an antagonist of XIAP anti-Caspase activity. |
| Liston P, Fong WG, Kelly NL, Toji S, Miyazaki T, Conte D, Tamai K, Craig CG, McBurney MW, Korneluk RG |
| Nature cell biology. 2001 ; 3 (2) : 128-133. |
| PMID 11175744 |
| Low expression of XIAP-associated factor 1 in human colorectal cancers. |
| Ma TL, Ni PH, Zhong J, Tan JH, Qiao MM, Jiang SH |
| Chinese journal of digestive diseases. 2005 ; 6 (1) : 10-14. |
| PMID 15667552 |
| XAF1 expression is significantly reduced in human melanoma. |
| Ng KC, Campos EI, Martinka M, Li G |
| The Journal of investigative dermatology. 2004 ; 123 (6) : 1127-1134. |
| PMID 15610524 |
| Motoneuron resistance to apoptotic cell death in vivo correlates with the ratio between X-linked inhibitor of apoptosis proteins (XIAPs) and its inhibitor, XIAP-associated factor 1. |
| Perrelet D, Perrin FE, Liston P, Korneluk RG, MacKenzie A, Ferrer-Alcon M, Kato AC |
| The Journal of neuroscience : the official journal of the Society for Neuroscience. 2004 ; 24 (15) : 3777-3785. |
| PMID 15084658 |
| The role of XAF1 in cancer. |
| Plenchette S, Cheung HH, Fong WG, LaCasse EC, Korneluk RG |
| Current opinion in investigational drugs (London, England : 2000). 2007 ; 8 (6) : 469-476. |
| PMID 17621877 |
| Potent antitumor efficacy of XAF1 delivered by conditionally replicative adenovirus vector via caspase-independent apoptosis. |
| Qi R, Gu J, Zhang Z, Yang K, Li B, Fan J, Wang C, He Z, Qiao L, Lin Z, Liu XY |
| Cancer gene therapy. 2007 ; 14 (1) : 82-90. |
| PMID 17008933 |
| Adjuvant whole abdominal intensity modulated radiotherapy (IMRT) for high risk stage FIGO III patients with ovarian cancer (OVAR-IMRT-01) - Pilot trial of a phase I/II study: study protocol. |
| Rochet N, Jensen AD, Sterzing F, Munter MW, Eichbaum MH, Schneeweiss A, Sohn C, Debus J, Harms W |
| BMC cancer. 2007 ; 7 : page 227. |
| PMID 18093313 |
| All-trans retinoic acid induces XAF1 expression through an interferon regulatory factor-1 element in colon cancer. |
| Wang J, Peng Y, Sun YW, He H, Zhu S, An X, Li M, Lin MC, Zou B, Xia HH, Jiang B, Chan AO, Yuen MF, Kung HF, Wong BC |
| Gastroenterology. 2006 ; 130 (3) : 747-758. |
| PMID 16530516 |
| Xaf1 can cooperate with TNFalpha in the induction of apoptosis, independently of interaction with XIAP. |
| Xia Y, Novak R, Lewis J, Duckett CS, Phillips AC |
| Molecular and cellular biochemistry. 2006 ; 286 (1-2) : 67-76. |
| PMID 16432762 |
| Coexistence of high levels of apoptotic signaling and inhibitor of apoptosis proteins in human tumor cells: implication for cancer specific therapy. |
| Yang L, Cao Z, Yan H, Wood WC |
| Cancer research. 2003 ; 63 (20) : 6815-6824. |
| PMID 14583479 |
| Identification of a novel splice variant of X-linked inhibitor of apoptosis-associated factor 1. |
| Yin W, Cheepala S, Clifford JL |
| Biochemical and biophysical research communications. 2006 ; 339 (4) : 1148-1154. |
| PMID 16343440 |
| Correlation between the single-site CpG methylation and expression silencing of the XAF1 gene in human gastric and colon cancers. |
| Zou B, Chim CS, Zeng H, Leung SY, Yang Y, Tu SP, Lin MC, Wang J, He H, Jiang SH, Sun YW, Yu LF, Yuen ST, Kung HF, Wong BC |
| Gastroenterology. 2006 ; 131 (6) : 1835-1843. |
| PMID 17087954 |
| Citation |
| This paper should be referenced as such : |
| Plenchette, S ; Fong, WG ; Korneluk, RG |
| XAF1 (XIAP associated factor-1) |
| Atlas Genet Cytogenet Oncol Haematol. 2008;12(5):397-399. |
| Free journal version : [ pdf ] [ DOI ] |
| On line version : http://AtlasGeneticsOncology.org/Genes/XAF1ID44095ch17p13.html |
| Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 1 ] |
|
Lung: Translocations in Adenocarcinoma
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| External links |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Fri Jun 30 11:21:36 CEST 2017 |
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