| Written | 2010-11 | Michael R Dohn, Albert B Reynolds |
| Department of Cancer Biology, Vanderbilt University, Nashville, TN, USA |
| Identity |
| Alias_symbol (synonym) | ZNF-kaiso |
| kaiso | |
| WUGSC:H_DJ525N14.1 | |
| KAISO | |
| ZNF348 | |
| Other alias | |
| HGNC (Hugo) | ZBTB33 |
| LocusID (NCBI) | 10009 |
| Atlas_Id | 43785 |
| Location | Xq24 [Link to chromosome band Xq24] |
| Location_base_pair | Starts at 120250755 and ends at 120258396 bp from pter ( according to hg19-Feb_2009) [Mapping ZBTB33.png] |
| Fusion genes (updated 2017) | Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands) |
| YWHAZ (8q22.3) / ZBTB33 (Xq24) | ZBTB33 (Xq24) / ZBTB33 (Xq24) |
| DNA/RNA |
 | |
| ZBTB33/Kaiso genomic sequence (7.64 Kb) is composed of three exons (green). The coding region (red) is within exon 3. | |
| Description | DNA consists of three exons, the third of which contains the coding region. |
| Transcription | Transcription of this gene produces transcript variants 1 (5324 bp) and 2 (5225 bp) that encode the same protein. Variant 2 lacks exon 2 in the 5' UTR. |
| Pseudogene | None. |
| Protein |
 | |
| ZBTB33/Kaiso contains an N-terminal POZ/BTB domain (green), two acidic regions (blue), and three C-terminal zinc finger domains (red). | |
| Description | ZBTB33/Kaiso (hereafter Kaiso) is a member of the BTB/POZ (Broad complex, Tramtrak, Bric á brac/Pox virus and zinc finger)-zinc finger family of transcription factors. Kaiso was originally identified in a yeast two-hybrid screen as a binding partner for the Armadillo repeat domain protein p120-catenin (CTNND1) and has subsequently been found to also interact with the p120-catenin-related protein delta-catenin. The N-terminal POZ/BTB domain mediates Kaiso interactions with N-CoR, the CTC-binding factor (CTCF), and Znf131, as well as Kaiso homodimerization. |
| Expression | Kaiso is ubiquitously expressed. |
| Localisation | In various mammalian cell lines Kaiso localizes nearly exclusively to the nucleus, but in normal and tumor tissues Kaiso is predominantly detected in the cytoplasm. During mitosis a pool of Kaiso localizes to microtubles and centrosomes. |
| Function | Via its zinc finger domain, Kaiso binds DNA and functions as both a repressor and activator of transcription. Kaiso recognizes methylated CpG dinucleotides as well as a sequence-specific site (TCCTGCNA). While several genes are repressed by Kaiso (including matrilysin, siamois, c-Fos, cyclin-D1, c-Myc, Wnt11, MMP-7 and MTA2), rapsyn is the only reported gene to be activated by Kaiso. |
| Homology | Mus musculus - Zbtb33; Rattus norvegicus - Zbtb33; Xenopus laevis - zbtb33; Danio rerio - zbtb33; Pan troglodytes - ZBTB33; Bos Taurus - ZBTB33; Gallus gallus - ZBTB33. |
| Mutations |
| Note | None reported. |
| Implicated in |
| Note | |
| Entity | Lung cancer |
| Note | Immunohistochemical analysis of 294 cases of non-small cell lung cancer, including 50 cases of paired lymph node metastases, revealed a correlation of cytoplasmic Kaiso staining with poor prognosis, and shRNA-mediated knockdown of Kaiso enhances proliferative and invasive capabilities of several lung cancer cell lines. |
| Entity | Colon cancer |
| Note | Kaiso has been shown to repress expression of methylated tumor suppressor genes, and depletion of Kaiso sensitizes colon cancer cell lines to chemotherapy. Moreover, Kaiso is upregulated in intestinal tumors in mice, and a delayed onset of intestinal tumorigenesis is observed when Kaiso-null mice are crossed with the tumor-susceptible ApcMin/+ mice. |
| Entity | Gastric cancer |
| Note | A study of the Helicobacter pylori-induced inflammatory response, which, if persistent, increases the risk for gastric adenocarcinoma, revealed that H. pylori induces nuclear translocation of the Kaiso-binding partner p120-catenin. Nuclear p120-catenin then relieves Kaiso-mediated repression of MMP-7, which is often overexpressed in premalignant and malignant gastric lesions. |
| Entity | Vertebrate development |
| Note | Injection of Xenopus laevis embryos with morpholinos targeting xKaiso leads to a developmental delay during gastrulation. Initially, Kaiso's roles in both general transcription repression and in regulation of canonical and non-canonical Wnt-signaling were thought to contribute to this phenotype, but subsequent studies determined that Kaiso's main role in early Xenopus development is restricted to the maintenence of transcriptional silencing. However, disruption of the Kaiso gene in mice did not reveal any abnormalities in development or gene expression. |
| Bibliography |
| Cytoplasmic Kaiso is associated with poor prognosis in non-small cell lung cancer. |
| Dai SD, Wang Y, Miao Y, Zhao Y, Zhang Y, Jiang GY, Zhang PX, Yang ZQ, Wang EH. |
| BMC Cancer. 2009 Jun 9;9:178. |
| PMID 19508730 |
| The catenin p120(ctn) interacts with Kaiso, a novel BTB/POZ domain zinc finger transcription factor. |
| Daniel JM, Reynolds AB. |
| Mol Cell Biol. 1999 May;19(5):3614-23. |
| PMID 10207085 |
| The p120(ctn)-binding partner Kaiso is a bi-modal DNA-binding protein that recognizes both a sequence-specific consensus and methylated CpG dinucleotides. |
| Daniel JM, Spring CM, Crawford HC, Reynolds AB, Baig A. |
| Nucleic Acids Res. 2002 Jul 1;30(13):2911-9. |
| PMID 12087177 |
| Dancing in and out of the nucleus: p120(ctn) and the transcription factor Kaiso. |
| Daniel JM. |
| Biochim Biophys Acta. 2007 Jan;1773(1):59-68. Epub 2006 Sep 7. (REVIEW) |
| PMID 17050009 |
| The human enhancer blocker CTC-binding factor interacts with the transcription factor Kaiso. |
| Defossez PA, Kelly KF, Filion GJ, Perez-Torrado R, Magdinier F, Menoni H, Nordgaard CL, Daniel JM, Gilson E. |
| J Biol Chem. 2005 Dec 30;280(52):43017-23. Epub 2005 Oct 17. |
| PMID 16230345 |
| Kaiso regulates Znf131-mediated transcriptional activation. |
| Donaldson NS, Nordgaard CL, Pierre CC, Kelly KF, Robinson SC, Swystun L, Henriquez R, Graham M, Daniel JM. |
| Exp Cell Res. 2010 Jun 10;316(10):1692-705. Epub 2010 Mar 18. |
| PMID 20303951 |
| Non-canonical Wnt signals are modulated by the Kaiso transcriptional repressor and p120-catenin. |
| Kim SW, Park JI, Spring CM, Sater AK, Ji H, Otchere AA, Daniel JM, McCrea PD. |
| Nat Cell Biol. 2004 Dec;6(12):1212-20. Epub 2004 Nov 14. |
| PMID 15543138 |
| Kaiso contributes to DNA methylation-dependent silencing of tumor suppressor genes in colon cancer cell lines. |
| Lopes EC, Valls E, Figueroa ME, Mazur A, Meng FG, Chiosis G, Laird PW, Schreiber-Agus N, Greally JM, Prokhortchouk E, Melnick A. |
| Cancer Res. 2008 Sep 15;68(18):7258-63. |
| PMID 18794111 |
| p120 and Kaiso regulate Helicobacter pylori-induced expression of matrix metalloproteinase-7. |
| Ogden SR, Wroblewski LE, Weydig C, Romero-Gallo J, O'Brien DP, Israel DA, Krishna US, Fingleton B, Reynolds AB, Wessler S, Peek RM Jr. |
| Mol Biol Cell. 2008 Oct;19(10):4110-21. Epub 2008 Jul 23. |
| PMID 18653469 |
| Kaiso/p120-catenin and TCF/beta-catenin complexes coordinately regulate canonical Wnt gene targets. |
| Park JI, Kim SW, Lyons JP, Ji H, Nguyen TT, Cho K, Barton MC, Deroo T, Vleminckx K, Moon RT, McCrea PD. |
| Dev Cell. 2005 Jun;8(6):843-54. |
| PMID 15935774 |
| Kaiso-deficient mice show resistance to intestinal cancer. |
| Prokhortchouk A, Sansom O, Selfridge J, Caballero IM, Salozhin S, Aithozhina D, Cerchietti L, Meng FG, Augenlicht LH, Mariadason JM, Hendrich B, Melnick A, Prokhortchouk E, Clarke A, Bird A. |
| Mol Cell Biol. 2006 Jan;26(1):199-208. |
| PMID 16354691 |
| Regulation of the rapsyn promoter by kaiso and delta-catenin. |
| Rodova M, Kelly KF, VanSaun M, Daniel JM, Werle MJ. |
| Mol Cell Biol. 2004 Aug;24(16):7188-96. |
| PMID 15282317 |
| Kaiso is a genome-wide repressor of transcription that is essential for amphibian development. |
| Ruzov A, Dunican DS, Prokhortchouk A, Pennings S, Stancheva I, Prokhortchouk E, Meehan RR. |
| Development. 2004 Dec;131(24):6185-94. Epub 2004 Nov 17. |
| PMID 15548582 |
| The non-methylated DNA-binding function of Kaiso is not required in early Xenopus laevis development. |
| Ruzov A, Savitskaya E, Hackett JA, Reddington JP, Prokhortchouk A, Madej MJ, Chekanov N, Li M, Dunican DS, Prokhortchouk E, Pennings S, Meehan RR. |
| Development. 2009 Mar;136(5):729-38. Epub 2009 Jan 21. |
| PMID 19158185 |
| The transcriptional repressor Kaiso localizes at the mitotic spindle and is a constituent of the pericentriolar material. |
| Soubry A, Staes K, Parthoens E, Noppen S, Stove C, Bogaert P, van Hengel J, van Roy F. |
| PLoS One. 2010 Feb 15;5(2):e9203. |
| PMID 120169156 |
| Expression and nuclear location of the transcriptional repressor Kaiso is regulated by the tumor microenvironment. |
| Soubry A, van Hengel J, Parthoens E, Colpaert C, Van Marck E, Waltregny D, Reynolds AB, van Roy F. |
| Cancer Res. 2005 Mar 15;65(6):2224-33. |
| PMID 15781635 |
| The catenin p120ctn inhibits Kaiso-mediated transcriptional repression of the beta-catenin/TCF target gene matrilysin. |
| Spring CM, Kelly KF, O'Kelly I, Graham M, Crawford HC, Daniel JM. |
| Exp Cell Res. 2005 May 1;305(2):253-65. |
| PMID 15817151 |
| N-CoR mediates DNA methylation-dependent repression through a methyl CpG binding protein Kaiso. |
| Yoon HG, Chan DW, Reynolds AB, Qin J, Wong J. |
| Mol Cell. 2003 Sep;12(3):723-34. |
| PMID 14527417 |
| Citation |
| This paper should be referenced as such : |
| Dohn, MR ; Reynolds, AB |
| ZBTB33 (zinc finger, BTB domain containing 33) |
| Atlas Genet Cytogenet Oncol Haematol. 2011;15(7):605-607. |
| Free journal version : [ pdf ] [ DOI ] |
| On line version : http://AtlasGeneticsOncology.org/Genes/ZBTB33ID43785chXq24.html |
| Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ] |
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t(9;17)(p13;p12) PAX5/NCOR1
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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 : Thu Oct 12 16:37:18 CEST 2017 |
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