|Written||2011-07||Kalliopi Apostolopoulou, Ioannis S Pateras, Athanassios Kotsinas, Vassilis G Gorgoulis|
|University of Athens, Faculty of Medicine, Department of Histology, Embryology, Molecular Carcinogenesis Group, Athens, Greece|
(Note : for Links provided by Atlas : click)
|zinc finger and BTB domain containing 7|
|Location||19p13.3 [Link to chromosome band 19p13]|
|Location_base_pair||Starts at 4043304 and ends at 4066945 bp from pter ( according to hg19-Feb_2009) [Mapping ZBTB7A.png]|
|Local_order||- EEF2 (19pter-q12) eukaryotic translation elongation factor 2
- SNORD37 (19p13.3) small nucleolar RNA, C/D box 37
- PIAS4 (19p13.3) protein inhibitor of activated STAT, 4
- ZBTB7A (19p13.3) zinc finger and BTB domain containing 7A
- MAP2K2 (19q13.3) mitogen-activated protein kinase kinase 2
- CREB3L3 (19p13.3) cAMP responsive element binding protein 3-like 3
|Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)|
|TGFBR2 (3p24.1) / ZBTB7A (19p13.3)||TNK1 (17p13.1) / ZBTB7A (19p13.3)||ZBTB7A (19p13.3) / DKK2 (4q25)|
|ZBTB7A (19p13.3) / TNK1 (17p13.1)|
|Schematic diagram depicting the structure and 19p13.3 chromosomal localization of the ZBTB7A/POKEMON gene.|
|Description|| Size: 21601 bases. |
Orientation: minus strand.
Cloning of the 5'-upstream region of ZBTB7A revealed: a) the absence of putative TATA and CCAAT sequences, b) the presence of two consensus sequences for the binding transcription factor Sp1, SpA (-641~636-) and SpB (-972~-967), as well as consensus sequences for the AP-1, AP-2, PU.1, Hb, CBF-1, GATA-1 elements and p53-binding sites, c) the presence of three regulatory elements, POS-D, NEG-U and NEG-D, with a key role in the regulation of the Pokemon gene.
The nucleotide sequence from -83 to -71 contains the positive element POS-D, which is necessary for the strong activity of the Pokemon promoter. The region from -558 to -541 contains the NEG-U element, involved in the negative regulation of the Pokemon promoter. The region from -128 to -108, namely NEG-D, is also necessary for the negative regulation of the Pokemon promoter. Neither NEG-U nor NEG-D element alone can negatively affect Pokemon expression. Pokemon promoter activity is greatly dependent on the interaction (cooperation) between NEG-U and NEG-D elements. This synergistic inhibition on Pokemon expression requires a specific length between the regulatory elements. Once this distance is reduced, the interaction between the NEG-U and NEG-D elements is almost abolished.
|Transcription|| The gene is comprised of 3 exons, building a main transcript of 4456 bps.|
|Pseudogene||There are no known pseudogenes.|
|Schematic representation of human ZBTB7A protein structure. POZ domain: 24-131, ZF: 376-489, NLS: 489-503.|
|Description|| ZBTB7A protein is composed of 584 amino acids (a.a.) with a molecular weight of 86 kDa. It belongs to the POK (POZ and Krüppel) family of transcriptional repressors. Members of this family have a characteristic structure, containing a NH2-terminal POZ/BTB domain (poxvirus zinc finger/broad-complex tramtrack, bric-à-brac) and a COOH-terminal domain, consisting of C2H2 Krüppel-type zinc fingers, "surnamed" due to resemblance with the Drosophila segmentation protein Krüppel. Due to this structure, they are also known as POZ/ZF proteins. At the C-terminus a bipartite nuclear localization signal (NLS) is located.|
POZ/BTB domain represents a 120 a.a. evolutionary conserved domain, present in more than 200 human proteins, which mediates protein-protein interactions. It is responsible for homodimerization as well as heterodimerization mediating the recruitment of corepressor complexes, such as nuclear co-repressor (N-CoR), silencing mediator of retinoic acid (SMRT), B-CoR (Bcl-6 co-repressor), mSin3A (SIN3 homolog A, transcription regulator) to the target genes. This also facilitates the binding of histone deacetylases within the target genes leading to its transcriptional repression. It also interacts with Sp1 zinc finger proteins.
C2H2 Krüppel-type zinc finger domain, found in more than 600 human proteins, represents a 25-30 a.a. domain, responsible for specific DNA recognition and binding. It is characterised by two conserved cysteine and histidine residue pairs that coordinate a single zinc atom.
|Expression||ZBTB7A is expressed in all proliferating cells. ZBTB7A is highly expressed in malignant tissues than in the corresponding benign or normal tissue (breast, lung, prostate).|
|Localisation||ZBTB7A is constitutively nuclear, due to a Nuclear Localization Signal (NLS) located at the C-terminus (a.a. 498-502). Immunohistochemical (IHC) studies of ZBTB7A expression in NSCLCs (Non-small cell lung carcinomas) have shown a nuclear signal. In NSCLCs the immunostaining is prevalent in the cancerous nests, whereas few tumour-associated stromal cells and a small number of parabasal intermediate cells in the adjacent normal bronchial epithelium, are positively stained. ZBTB7A nuclear expression was also prevalent in malignant breast tissues and surrounding fibroblasts and lymphocytes, whereas stromal cells were weakly stained.|
|Function|| ZBTB7A has a variety of biological functions. ZBTB7A was originally identified as a factor binding to a specific sequence within the human immunodeficiency virus, type 1 promoter, and can physically interact with other POK family members such as BCL-6. Co-expression of ZBTB7A and BCL-6 in lymphoma, predicts the clinical outcome. ZBTB7A is also implicated in differentiation processes like osteoclastogenesis, chondrogenesis and adipogenesis. Furthermore, ZBTB7A knockdown in mice, results in embryonic lethality due to severe anaemia and impaired cellular differentiation. |
ZBTB7A is a transcription factor which regulates the expression of many proteins, such as extracellular matrix collagen types I, II, IX, X and XI, fibronectin, elastin, human cartilage oligomeric matrix protein, p19ARF tumour suppressor and the c-fos and c-myc oncoproteins by binding to consensus sequence within their promoters. ZBTB7A preferable binding sites include either a single guanine-rich site or two half-sites, each with the consensus sequence G(A/G)GGG(T/C)(C/T)(T/C)(C/T), with a variety in spacing and orientation, supporting that ZBTB7A can bind to the DNA with great flexibility. In other cases, the interaction between Pokemon POZ domain and other transcription factors, such as Sp-1 or the p65 subunit of NF-kappaB, is necessary for its regulatory role.
ZBTB7A self-associates, as depicted in vivo and in vitro, via both its POZ domain and its zinc finger (ZF) domain. ZBTB7A can act as a transcriptional repressor or activator depending on the promoter context.
Finally, it plays a crucial role in cell tumorigenesis.
- Transcription regulator
1. ZBTB7A/FBI-1 + IST (HIV)
2. FBI-1 + adipogenesis
3. FBI-1 + FASN (transcriptional activator)
4. FBI-1 + NF-kappaB (transcriptional activator)
5. FBI-1 + ADH5/FDH (transcriptional repressor)
6. ZBTB7A + ARF (transcriptional repressor)
7. FBI-1 + p21WAF1/CIP1 (transcriptional repressor)
8. FBI-1 + CCS-3 + p21WAF1/CIP1
9. LRF - COMP (transcriptional repressor)
10. FBI1 - AR (transcriptional repressor)
11. Pokemon - survivin (transcriptional activator)
- Relation with ASF/SF2 through miRNAs
LRF is regulated by microRNA (miRNA) families.
- Relation with anticancer agents
Curcumin is a natural compound known for its antioxidant, anti-inflammatory and anticarcinogenic properties, since it can inhibit the proliferation and induce the apoptosis of cancer cells, such as gastric, colon, breast. Curcumin inhibits ZBTB7A transcriptional activation, by suppressing the Sp1 stimulatory effect on Pokemon promoter, as it inhibits Sp1 recruitment to the Pokemon promoter.
- Global mapping of ZBTB7A downstream target genes in HepG2 cells
ChIP-on-chip analysis performed in the human hepato-carcinoma cancer cell line HepG2, revealed 556 genes as potential direct targets of ZBTB7A. These genes are mainly divided in three categories: genes regulating metabolism, transcriptional regulators and cell signal transduction genes. Among the most ZBTB7A-targeted metabolic pathways are the aminosugar, arachidonic acid, tryptophan, pyrimidine and purine metabolic pathways. Moreover sucrose, vitamin B6, valine, leucine and isoleucine, folate, fatty acid and glycerolipid metabolism, are characterized as ZBTB7A regulatory targets. As far as signal transduction is concerned, ZBTB7A might play a regulatory role on the MAPK signalling pathway. Furthermore, four genes involved in axon guidance, a key stage in the formation of the neuronal network, are directly regulated by ZBTB7A expression in HepG2 cells. This pinpoints to a potential regulatory role for ZBTB7A in neural development.
- ZBTB7A and SUMOylation
ZBTB7A can be sumoylated as it contains an amino-acid sequence highly similar to the SUMO-1 conjugate consensus motif, ψKXE (ψ: large hydrophobic residue, K: lysine to which SUMO-1 is conjugated, X: any amino acid, and E: glutamic acid). Sumoylation of several lysine residues of ZBTB7A is important in order to achieve full repressive activity.
|Homology|| LRF (leukemia/lymphoma-related factor) is the mouse homologue of FBI-1. It co-immunoprecipitates and co-localizes with Bcl-6 and is involved in chondrogenesis and adipogenesis.|
OCZF (osteoclast-derived zinc finger), the rat homologue of FBI-1, is a transcription repressor, involved in osteoclastogenesis. Mouse LRF and rat OCZF are 90 and 96% identical at the nucleotide and amino acid levels, respectively. Mouse LRF and human FBI-1 sequences are 89% identical at the amino acid level.
|Note||No known mutations.|
5. Implicated in
|Note|| Since ZBTB7A specifically represses transcription of p14ARF, a major tumor suppressor gene, it was characterized as a potential proto-oncogene, expected to play a significant role in carcinogenesis. ZBTB7A null MEFs (ZBTB7A-/-) had higher p19ARF protein levels than wild-type MEFs and resisted to proliferation and transformation upon oncogenic stimulation. The oncogenic nature of ZBTB7A was also examined in vivo in transgenic mice, which overexpressed ZBTB7A in T and B lymphoid lineage cells. These mice developed thymic lymphomas and tumour infiltration into bone marrow and poor survival compared to the wild-type ones.|
ZBTB7A is overexpressed in diffuse large B cell lymphomas (DLBCL) and follicular lymphomas, as well as in anaplastic large cell lymphoma and angioimmunoblastic lymphoma, as far as T-cell malignancies are concerned.
ZBTB7A oncogenic role in human malignant gliomas was revealed with comparative genomic hybridization analysis (bioinformatics methods).
Tissue microarray analysis revealed ZBTB7A overexpression in colon, prostate, bladder, as well as in breast and lung carcinomas.
IHC and immunofluorescence analysis revealed a significantly higher expression of LRF protein in malignant breast specimens than in the corresponding benign or normal tissue, with a clear nuclear expression pattern. 40% and 15% of benign breast biopsy tissues expressed LRF mRNA transcripts and protein, respectively, probably because they contain premalignant cells and adipocytes.
Ductal hyperplasia showed weak LRF staining, whereas in invasive ductal carcinoma and invasive lobular carcinoma strong nuclear expression of LRF was observed.
In breast cancer tissues ZBTB7A expression levels were significantly correlated with histological grade, implying a potential role of ZBTB7A in breast cancer development, whereas were inversely correlated with the oestrogen receptor status. No correlation was confirmed between ZBTB7 overexpression and tumour size, stage, lymph node status, or PR status. However its overexpression predicted poorer overall survival and was associated with shorter recurrence-free survival. In addition, ZBTB7A is expressed in the nuclei of human colon, renal, hepatocellular carcinomas, mesotheliomas and thymoma tumor cells.
IHC and immunoblotting analysis showed ZBTB7A overexpression in NSCLC specimens, compared to adjacent normal tissue elements. Gene amplification proved to be a relatively frequent event leading to ZBTB7A overproduction in NSCLCs. Furthermore, a positive correlation between ZBTB7A expression and proliferation, as well as tumour size, was revealed. Survival analysis correlated ZBTB7A overexpression with poor prognosis. ZBTB7A expression is not associated with the NSCLC patients' sex, age, lymph node stage, tumor differentiation degree and histology.
Furthermore IHC, immunoblotting and PCR analysis revealed significantly higher ZBTB7A (FBI-1) protein and mRNA expression levels in ovarian cancer samples and cell lines, compared to benign or borderline tumours. Gene amplification was proved to be, to a great proportion, the underlying mechanism of ZBTB7A overexpression in ovarian cancers. Upregulated ZBTB7A expression was found in metastatic foci and malignant ascites and was associated with advanced stage, poor overall survival and disease-free survival. Additionally, it was shown that ZBTB7A plays an important role in ovarian cancer cell migration, proliferation and invasiveness, through its direct binding to the promoter of MT1-MMP (membrane type 1-matrix metalloproteinase), which enhances MT1-MMP promoter activity.
Moreover, ZBTB7A (LRF) is implicated in the pathogenesis of prostate cancer, since IHC, Western blot and PCR analyses revealed a significantly higher expression of LRF mRNA transcripts and protein in prostate cancer (PC) specimens than in benign prostate hyperplasia (BPH). A significant increase in LRF mRNA transcripts and protein levels was observed when normal human prostate cells (RWPE-1) as well as prostate cancer cells, (LNCaP androgen sensitive prostate cancer cells and PC-3 androgen-insensitive prostate cancer cells), were treated with EGF (epidermal growth factor).
Recently, the development of a novel strategy for silencing Pokemon in vivo, with promising results, provided a marked anti-tumour activity in nude mice.
|Entity||Cell growth and proliferation|
|Note|| ZBTB7A is implicated in cell growth regulation, as it transcriptionaly represses Rb (Retinoblastoma), a gene involved in differentiation, cell cycle control, and tumor suppression. FBI-1, through its POZ domain, recruits HDACs to deacetylate histones H3 and H4 around the Rb proximal promoter region, resulting in Rb transcriptional repression. Additionally, FBI-1 binds to the 4 FREs (FBI-1 binding sites, GC-rich) on the Rb promoter and relatively strongly to the FRE2 element.|
FBI-1 enhances cellular transformation as well. FBI-1 overexpression in HeLa cells resulted in formation of large foci and increased the number of HeLa cells in S phase. Moreover ZBTB7A is involved in cell proliferation in MEFs.
|Note|| ZBTB7A is implicated in many differentiation processes including osteoclastogenesis, chondrogenesis and adipogenesis. ZBTB7A knockdown in mice resulted in embryonic lethality due to severe anaemia and impaired cellular differentiation. LRF was found to be essential for terminal fetal erythropoiesis. LRF is a downstream target of GATA1. GATA1 is a transcription factor significant for erythroblasts differentiation, maturation and protection from apoptosis. GATA1 binds directly to the two putative GATA-binding sites in ZBTB7A promoter region and activates its expression. Additionally, in the absence of LRF, both in embryos and adults, BIM a significant apoptosis inducer in hematopoietic cells was markedly upregulated. LRF directly binds to BIM proximal promoter region, which contains four potential LRF binding sites and represses its expression, during the late stages of erythroid differentiation. On the other hand, BIM loss rescues LRF knockout mice from fetal anemia.|
From the above, it is resumed that the suppression of BIM-mediated apoptosis by LRF, which in turn is activated by GATA-1, is critical for effective erythropoiesis.
RANK and its ligand, RANKL (a member of the tumor necrosis factor - TNF superfamily), are critical molecules in osteoclastogenesis. RANKL also plays an important role in inflammatory bone loss. FBI-1/OCZF/LRF is highly expressed in osteoclasts and is an important regulator of RANKL-induced osteoclastogenesis. LRF siRNA inhibits osteoclast differentiation. Osteoclast formation is a crucial step in bone destruction in chronic arthritis. FBI-1/OCZF is highly expressed in osteoclasts in inflammatory arthritis, implying a role in inflammatory bone erosion. The above suggest that by enhancing osteoclastogenesis and survival of osteoclasts, FBI-1/OCZF/LRF might play important roles in bone destruction in vivo, including the bone loss and remodelling that occurs in chronic inflammatory arthropathies, such as rheumatoid arthritis.
|Entity||Regulation of B lymphopoiesis|
|Note|| LRF (mouse homologue of ZBTB7A) regulates B lymphocytes development from lymphoid-restricted progenitors in mice, versus T lymphoid fate. Knockdown of LRF in HSCs (hematopoietic stem cells) and CLPs (common lymphoid progenitors), impaired B cell development and resulted in extrathymic T cell development in the bone marrow (BM). Furthermore, LRF blocks Notch signalling pathway in normal HSCs. This pathway is essential for T cell development. Notch deletion in mouse HSCs results in a decreased number of thymic T cells, whereas it enhances B cell development in the thymus. |
Moreover, LRF regulates mature B cell lineage fate and humoral immune responses, through the obligatory formation of a dimer in B cells, important for its function. Furthermore, LRF inactivation in transformed B cells attenuated their growth rate. The above suggest the potential targeting of LRF dimmers as a treatment of autoimmune diseases and B cell malignancies.
|Entity||LRF bypasses RASV12-induced senescence|
|Note||LRF enhances E2F-dependent transcription, with an unknown mechanism, which does not include Rb downregulation. LRF synergizes with RASV12 in inducing E2F. LRF bypasses RASV12-induced senescence by activating E2F-target genes, such as Cyclin E, Cyclin A and p107. Specifically, Cyclin E is shown to be indispensable, but not sufficient for LRF-mediated bypass of RASV12-induced senescence. The above mentioned bypass occurs independently of critical senescence inducers, such as p19ARF, p21CIP and p16INK4A.|
|Entity||LRF is post-transcriptionally controlled by MiR-20a: implications in senescence|
|Note|| MicroRNAs (miRNAs) are short 20-22 nucleotide RNA molecules, which act as post-transcriptional suppressors. They repress mRNA translation by base pairing to 3'UTR sequences.|
Mir-20a, a member of miR-17-92 cluster, can interact directly with ZBTB7A 3'UTR. Upon miR-20a overexpression in MEFs, LRF protein is reduced by 40%. Conversely, miR-20a depletion resulted in increased LRF protein levels by 55%.
MiR-20a induces p19ARF expression to a smaller extent than siLRF. However, miR-20a is a more efficient senescence inducer than siLRF, implying the contribution of other factors to the senescence effect.
It has been shown that E2F1 expression is also under the miR-20a control in MEFs. When miR-20a is highly expressed there is a decrease in E2F1 protein levels, to a greater degree than that after siLRF. Conversely, miR-20a depletion slightly enhances E2F1 expression. However, E2F1 silencing by siE2F1 in MEFs is not enough to induce senescence, whereas miR-20a overexpression in LRF-null MEF, with the concomitant E2F1 downregulation, significantly enhances senescence. In addition, miR-20a and not siLRF, can also increase p16INK4A protein levels, a key player in senescence pathway, both in wild type and LRF-null MEFs.
The above data support the notion that miR-20a elicited cellular senescence results mainly from LRF downregulation and consequent p19ARF upregulation, with the contribution of E2F1 down-regulation and p16INK4A induction.
|Entity||P-glycoprotein (Pgp) and transcriptional repression of Pokemon|
|Note||Pgp is a 170 kD protein, encoded by the human MDR1 (ABCB1) gene and belongs to the ATP-binding cassette transporters family. Pgp and the other family members function as pumps to extrude anticancer drugs from cancer cells and are related to drug resistance phenotype. Pgp is often over-expressed in drug-resistant cancer cells. It has been found that Pgp represses the transcription of Pokemon, through decreasing Pokemon promoter activity. Furthermore, this Pgp regulated suppression of Pokemon is p53 dependent.|
|Expression of leukemia/lymphoma-related factor (LRF/POKEMON) in human breast carcinoma and other cancers.|
|Aggarwal A, Hunter WJ 3rd, Aggarwal H, Silva ED, Davey MS, Murphy RF, Agrawal DK.|
|Exp Mol Pathol. 2010 Oct;89(2):140-8. Epub 2010 May 21.|
|Expression of leukemia/lymphoma related factor (LRF/Pokemon) in human benign prostate hyperplasia and prostate cancer.|
|Aggarwal H, Aggarwal A, Hunter WJ 3rd, Yohannes P, Khan AU, Agrawal DK.|
|Exp Mol Pathol. 2011b Apr;90(2):226-30. Epub 2011 Jan 18.|
|Gene amplification is a relatively frequent event leading to ZBTB7A (Pokemon) overexpression in non-small cell lung cancer.|
|Apostolopoulou K, Pateras IS, Evangelou K, Tsantoulis PK, Liontos M, Kittas C, Tiniakos DG, Kotsinas A, Cordon-Cardo C, Gorgoulis VG.|
|J Pathol. 2007 Nov;213(3):294-302.|
|Proto-oncogene FBI-1 represses transcription of p21CIP1 by inhibition of transcription activation by p53 and Sp1.|
|Choi WI, Jeon BN, Yun CO, Kim PH, Kim SE, Choi KY, Kim SH, Hur MW.|
|J Biol Chem. 2009a May 8;284(19):12633-44. Epub 2009 Feb 25.|
|Eukaryotic translation initiator protein 1A isoform, CCS-3, enhances the transcriptional repression of p21CIP1 by proto-oncogene FBI-1 (Pokemon/ZBTB7A).|
|Choi WI, Kim Y, Kim Y, Yu MY, Park J, Lee CE, Jeon BN, Koh DI, Hur MW.|
|Cell Physiol Biochem. 2009b;23(4-6):359-70. Epub 2009 May 6.|
|Functional analysis of the role of POK transcriptional repressors.|
|Brief Funct Genomic Proteomic. 2007 Mar;6(1):8-18. Epub 2007 Mar 24. (REVIEW)|
|Curcumin decreases the expression of Pokemon by suppressing the binding activity of the Sp1 protein in human lung cancer cells.|
|Cui J, Meng X, Gao X, Tan G.|
|Mol Biol Rep. 2010 Mar;37(3):1627-32. Epub 2009 May 15.|
|FBI-1 functions as a novel AR co-repressor in prostate cancer cells.|
|Cui J, Yang Y, Zhang C, Hu P, Kan W, Bai X, Liu X, Song H.|
|Cell Mol Life Sci. 2011 Mar;68(6):1091-103. Epub 2010 Sep 2.|
|Novel BTB/POZ domain zinc-finger protein, LRF, is a potential target of the LAZ-3/BCL-6 oncogene.|
|Davies JM, Hawe N, Kabarowski J, Huang QH, Zhu J, Brand NJ, Leprince D, Dhordain P, Cook M, Morriss-Kay G, Zelent A.|
|Oncogene. 1999 Jan 14;18(2):365-75.|
|P-Glycoprotein/MDR1 Regulates Pokemon Gene Transcription Through p53 Expression in Human Breast Cancer Cells.|
|He S, Liu F, Xie Z, Zu X, Xu W, Jiang Y.|
|Int J Mol Sci. 2010 Aug 27;11(9):3309-051.|
|Proto-oncogene FBI-1 (Pokemon/ZBTB7A) represses transcription of the tumor suppressor Rb gene via binding competition with Sp1 and recruitment of co-repressors.|
|Jeon BN, Yoo JY, Choi WI, Lee CE, Yoon HG, Hur MW.|
|J Biol Chem. 2008 Nov 28;283(48):33199-210. Epub 2008 Sep 18.|
|Overexpression of proto-oncogene FBI-1 activates membrane type 1-matrix metalloproteinase in association with adverse outcome in ovarian cancers.|
|Jiang L, Siu MK, Wong OG, Tam KF, Lam EW, Ngan HY, Le XF, Wong ES, Chan HY, Cheung AN.|
|Mol Cancer. 2010 Dec 21;9:318.|
|POZ for effect--POZ-ZF transcription factors in cancer and development.|
|Kelly KF, Daniel JM.|
|Trends Cell Biol. 2006 Nov;16(11):578-87. Epub 2006 Sep 22. (REVIEW)|
|The transcription factor FBI-1/OCZF/LRF is expressed in osteoclasts and regulates RANKL-induced osteoclast formation in vitro and in vivo.|
|Kukita A, Kukita T, Nagata K, Teramachi J, Li YJ, Yoshida H, Miyamoto H, Gay S, Pessler F, Shobuike T.|
|Arthritis Rheum. 2011 Sep;63(9):2744-54. doi: 10.1002/art.30455.|
|Transcription factor FBI-1 acts as a dual regulator in adipogenesis by coordinated regulation of cyclin-A and E2F-4.|
|Laudes M, Bilkovski R, Oberhauser F, Droste A, Gomolka M, Leeser U, Udelhoven M, Krone W.|
|J Mol Med (Berl). 2008 May;86(5):597-608. Epub 2008 Mar 27.|
|Role of the POZ zinc finger transcription factor FBI-1 in human and murine adipogenesis.|
|Laudes M, Christodoulides C, Sewter C, Rochford JJ, Considine RV, Sethi JK, Vidal-Puig A, O'Rahilly S.|
|J Biol Chem. 2004 Mar 19;279(12):11711-8. Epub 2003 Dec 30.|
|FBI-1 enhances transcription of the nuclear factor-kappaB (NF-kappaB)-responsive E-selectin gene by nuclear localization of the p65 subunit of NF-kappaB.|
|Lee DK, Kang JE, Park HJ, Kim MH, Yim TH, Kim JM, Heo MK, Kim KY, Kwon HJ, Hur MW.|
|J Biol Chem. 2005 Jul 29;280(30):27783-91. Epub 2005 May 24.|
|POZ domain transcription factor, FBI-1, represses transcription of ADH5/FDH by interacting with the zinc finger and interfering with DNA binding activity of Sp1.|
|Lee DK, Suh D, Edenberg HJ, Hur MW.|
|J Biol Chem. 2002 Jul 26;277(30):26761-8. Epub 2002 May 9.|
|Leukemia/lymphoma-related factor, a POZ domain-containing transcriptional repressor, interacts with histone deacetylase-1 and inhibits cartilage oligomeric matrix protein gene expression and chondrogenesis.|
|Liu CJ, Prazak L, Fajardo M, Yu S, Tyagi N, Di Cesare PE.|
|J Biol Chem. 2004 Nov 5;279(45):47081-91. Epub 2004 Aug 26.|
|The transcription factor Pokemon: a new key player in cancer pathogenesis.|
|Maeda T, Hobbs RM, Pandolfi PP.|
|Cancer Res. 2005b Oct 1;65(19):8575-8. (REVIEW)|
|LRF is an essential downstream target of GATA1 in erythroid development and regulates BIM-dependent apoptosis.|
|Maeda T, Ito K, Merghoub T, Poliseno L, Hobbs RM, Wang G, Dong L, Maeda M, Dore LC, Zelent A, Luzzatto L, Teruya-Feldstein J, Weiss MJ, Pandolfi PP.|
|Dev Cell. 2009 Oct;17(4):527-40.|
|Regulation of B versus T lymphoid lineage fate decision by the proto-oncogene LRF.|
|Maeda T, Merghoub T, Hobbs RM, Dong L, Maeda M, Zakrzewski J, van den Brink MR, Zelent A, Shigematsu H, Akashi K, Teruya-Feldstein J, Cattoretti G, Pandolfi PP.|
|Science. 2007 May 11;316(5826):860-6.|
|Critical residues within the BTB domain of PLZF and Bcl-6 modulate interaction with corepressors.|
|Melnick A, Carlile G, Ahmad KF, Kiang CL, Corcoran C, Bardwell V, Prive GG, Licht JD.|
|Mol Cell Biol. 2002 Mar;22(6):1804-18.|
|FBI-1, a factor that binds to the HIV-1 inducer of short transcripts (IST), is a POZ domain protein.|
|Morrison DJ, Pendergrast PS, Stavropoulos P, Colmenares SU, Kobayashi R, Hernandez N.|
|Nucleic Acids Res. 1999 Mar 1;27(5):1251-62.|
|FBI-1 can stimulate HIV-1 Tat activity and is targeted to a novel subnuclear domain that includes the Tat-P-TEFb-containing nuclear speckles.|
|Pendergrast PS, Wang C, Hernandez N, Huang S.|
|Mol Biol Cell. 2002 Mar;13(3):915-29.|
|Flexible DNA binding of the BTB/POZ-domain protein FBI-1.|
|Pessler F, Hernandez N.|
|J Biol Chem. 2003 Aug 1;278(31):29327-35. Epub 2003 May 15.|
|Purification and characterization of FBI-1, a cellular factor that binds to the human immunodeficiency virus type 1 inducer of short transcripts.|
|Pessler F, Pendergrast PS, Hernandez N.|
|Mol Cell Biol. 1997 Jul;17(7):3786-98.|
|The proto-oncogene LRF is under post-transcriptional control of MiR-20a: implications for senescence.|
|Poliseno L, Pitto L, Simili M, Mariani L, Riccardi L, Ciucci A, Rizzo M, Evangelista M, Mercatanti A, Pandolfi PP, Rainaldi G.|
|PLoS One. 2008 Jul 2;3(7):e2542.|
|ZBTB7 overexpression contributes to malignancy in breast cancer.|
|Qu H, Qu D, Chen F, Zhang Z, Liu B, Liu H.|
|Cancer Invest. 2010 Jul;28(6):672-8.|
|Regulation of pokemon 1 activity by sumoylation.|
|Roh HE, Lee MN, Jeon BN, Choi WI, Kim YJ, Yu MY, Hur MW.|
|Cell Physiol Biochem. 2007;20(1-4):167-80.|
|Pokemon expression in malignant glioma: an application of bioinformatics methods.|
|Rovin RA, Winn R.|
|Neurosurg Focus. 2005 Oct 15;19(4):E8.|
|The LRF transcription factor regulates mature B cell development and the germinal center response in mice.|
|Sakurai N, Maeda M, Lee SU, Ishikawa Y, Li M, Williams JC, Wang L, Su L, Suzuki M, Saito TI, Chiba S, Casola S, Yagita H, Teruya-Feldstein J, Tsuzuki S, Bhatia R, Maeda T.|
|J Clin Invest. 2011 Jul 1;121(7):2583-98. doi: 10.1172/JCI45682. Epub 2011 Jun 6.|
|Structure of the POZ domain of human LRF, a master regulator of oncogenesis.|
|Schubot FD, Tropea JE, Waugh DS.|
|Biochem Biophys Res Commun. 2006 Dec 8;351(1):1-6. Epub 2006 Oct 9.|
|Crystal structure of the BTB domain from the LRF/ZBTB7 transcriptional regulator.|
|Stogios PJ, Chen L, Prive GG.|
|Protein Sci. 2007 Feb;16(2):336-42. Epub 2006 Dec 22.|
|Tumor-targeted inhibition by a novel strategy - mimoretrovirus expressing siRNA targeting the Pokemon gene.|
|Tian Z, Wang H, Jia Z, Shi J, Tang J, Mao L, Liu H, Deng Y, He Y, Ruan Z, Li J, Wu Y, Ni B.|
|Curr Cancer Drug Targets. 2010 Dec;10(8):932-41.|
|MicroRNA (miRNA)-mediated interaction between leukemia/lymphoma-related factor (LRF) and alternative splicing factor/splicing factor 2 (ASF/SF2) affects mouse embryonic fibroblast senescence and apoptosis.|
|Verduci L, Simili M, Rizzo M, Mercatanti A, Evangelista M, Mariani L, Rainaldi G, Pitto L.|
|J Biol Chem. 2010 Dec 10;285(50):39551-63. Epub 2010 Oct 4.|
|Functional identification of LRF as an oncogene that bypasses RASV12-induced senescence via upregulation of CYCLIN E.|
|Vredeveld LC, Rowland BD, Douma S, Bernards R, Peeper DS.|
|Carcinogenesis. 2010 Feb;31(2):201-7. Epub 2009 Nov 25.|
|Cloning and functional analysis of 5'-upstream region of the Pokemon gene.|
|Yang Y, Zhou X, Zhu X, Zhang C, Yang Z, Xu L, Huang P.|
|FEBS J. 2008 Apr;275(8):1860-73. Epub 2008 Mar 18.|
|Overexpression of Pokemon in non-small cell lung cancer and foreshowing tumor biological behavior as well as clinical results.|
|Zhao ZH, Wang SF, Yu L, Wang J, Chang H, Yan WL, Zhang J, Fu K.|
|Lung Cancer. 2008b Oct;62(1):113-9. Epub 2008 Jun 11.|
|Pro-oncogene Pokemon promotes breast cancer progression by upregulating survivin expression.|
|Zu X, Ma J, Liu H, Liu F, Tan C, Yu L, Wang J, Xie Z, Cao D, Jiang Y.|
|Breast Cancer Res. 2011 Mar 10;13(2):R26. [Epub ahead of print]|
|Global mapping of ZBTB7A transcription factor binding sites in HepG2 cells.|
|Zu X, Yu L, Sun Y, Tian J, Liu F, Sun Q, He S, Sun G, Luo W, Jiang Y.|
|Cell Mol Biol Lett. 2010 Jun;15(2):260-71. Epub 2010 Mar 19.|
|This paper should be referenced as such :|
|Apostolopoulou, K ; Pateras, IS ; Kotsinas, A ; Gorgoulis, VG|
|ZBTB7A (zinc finger, BTB domain containing 7A)|
|Atlas Genet Cytogenet Oncol Haematol. 2011;15(12):1058-1066.|
|Free journal version : [ pdf ] [ DOI ]|
|On line version : http://atlasgeneticsoncology.usal.es/classic/Genes/ZBTB7AID42863ch19p13.html|
8. Other Leukemias implicated (Data extracted from papers in the Atlas) [ 4 ]
9. 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 : Thu Jan 17 19:12:22 CET 2019|
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