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Atlas of Genetics and Cytogenetics in Oncology and Haematology INIST-CNRS OPEN ACCESS JOURNAL Gene Section Short Communication CENPW (centromere protein W) Seyoung Jeon, Soojin Lee Department of Microbiology and Molecular Biology, Chungnam National Institute, 305-764, Daejeon, Republic of Korea (SJ, SL) Published in Atlas Database: June 2013 Online updated version : http://AtlasGeneticsOncology.org/Genes/CENPWID51452ch6q22.html DOI: 10.4267/2042/52069 This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence. © 2014 Atlas of Genetics and Cytogenetics in Oncology and Haematology Abstract: Short communication on CENPW, with data on DNA/RNA, on the protein encoded and where the gene is implicated. It contains a typical NLS sequence and histone fold region which is critical for binding to centromeric DNA. Identity Other names: C6orf173, CUG2 HGNC (Hugo): CENPW Location: 6q22.32 Expression Widely expressed; kidney, colon, breast, liver, lung, ovary, prostate, thyroid, etc. DNA/RNA Localisation Description Exons: 3, coding exons: 3, introns: 2. Intracellular, nucleus, centromere, kinetochore, nucleus matrix, nucleolus. Transcription Function Transcript length: 750 bps, open reading frame: 264 bps. CENP-W was originally identified as a cancerupregulated gene 2 (CUG2) which is commonly overexpressed in various human cancer tissues. Although it has high oncogenic activities, CENP-W also induces cell apoptosis when overexpressed in certain cell lines. After it was revealed that CENP-W forms a stable heterodimer with CENP-T and is localized in kinetochores during mitosis, CENP-W become recognized as a new member of the inner centromere protein complex. Subsequent studies have also shown that CENP-T-W-S-X forms a unique centromeric nucleosome-like heterotetramer structure which binds to and supercoils DNA. Pseudogene No pseudogene. Protein Description CENP-W gene encodes 88-amino acid protein which shows ~27% of amino acid sequence similarity to a general transcription repressor, human DR1. Figure 1. A genomic structure of the CENPW gene. Atlas Genet Cytogenet Oncol Haematol. 2014; 18(1) 5 CENPW (centromere protein W) Jeon S, Lee S Figure 2. Schematic representation of CENPW protein. Each domain is represented with the unique color and name. One nuclear localization signal (NLS) sequence of 17 amino acids starts at amino acid 13. Figure 3. mRNA expression of CUG2 in various tumors. DNA chip microarray profile in tumors (closed bar) and normal (open bar) tissues from the Gene Express Oncology DatasuiteTM of Gene Logic Inc. As a nucleolus-associated protein, CENP-W may play critical role in the formation of functional kinetochore, possibly by facilitating the recruitment of other centromeric components during interphase, which is required for proper chromosome segregation during mitosis. Implicated in Various human cancers Oncogenesis CENP-W has been found to be upregulated in several tumor tissues. When the expression level of CENP-W was examined by DNA chip microarray and RT-PCR in tumors, six tissues (ovary, liver, lung, pancreas, colon, and stomach) showed high-fold increases in expression profiles. Also, CENP-W-transformed NIH3T3 cells exhibited exceptionally prominent cancerous phenotypes in vitro as well as in vivo tumor forming assays. Homology According to NCBI-HomoloGene: Pan troglodytes (chimpanzee): centromere protein W (NP_001012525.1, 88 aa) Macacamulatta (Rhesus monkey): centromere protein W (XP_001107034.2, 88 aa) Canis lupus familiaris (dog): centromere protein W-like (XP_003638832.1, 88 aa) Bostaurus (cattle): centromere protein W (NP_001104731.1, 88 aa) Mus musculus (house mouse): centromere protein W (NP_001103217.1, 86 aa) Rattus norvegicus (Norway rat): centromere protein W (XP_001070657.1, 86 aa). References Lee S, Gang J, Jeon SB, Choo SH, Lee B, Kim YG, Lee YS, Jung J, Song SY, Koh SS. Molecular cloning and functional analysis of a novel oncogene, cancer-upregulated gene 2 (CUG2). Biochem Biophys Res Commun. 2007 Aug 31;360(3):633-9 Kim H, Lee M, Lee S, Park B, Koh W, Lee DJ, Lim DS, Lee S. Cancer-upregulated gene 2 (CUG2), a new component of centromere complex, is required for kinetochore function. Mol Cells. 2009 Jun 30;27(6):697-701 Mutations Note Over expressed in various cancer tissues; notably high in the ovary (6.3-fold), liver (6.0), lung (4.9), and pancreas (3.8). Atlas Genet Cytogenet Oncol Haematol. 2014; 18(1) Kim H, Lee S, Park B, Che L, Lee S. Sp1 and Sp3 mediate basal and serum-induced expression of human CENP-W. Mol Biol Rep. 2010 Oct;37(7):3593-600 6 CENPW (centromere protein W) Jeon S, Lee S Lee S, Koh W, Kim HT, Kim CH, Lee S. Cancer-upregulated gene 2 (CUG2) overexpression induces apoptosis in SKOV-3 cells. Cell Biochem Funct. 2010 Aug;28(6):461-8 CNS development in zebrafish. BMC Dev Biol. 2011 Aug 15;11:49 Prendergast L, van Vuuren C, Kaczmarczyk A, Doering V, Hellwig D, Quinn N, Hoischen C, Diekmann S, Sullivan KF. Premitotic assembly of human CENPs -T and -W switches centromeric chromatin to a mitotic state. PLoS Biol. 2011 Jun;9(6):e1001082 Park EH, Park EH, Cho IR, Srisuttee R, Min HJ, Oh MJ, Jeong YJ, Jhun BH, Johnston RN, Lee S, Koh SS, Chung YH. CUG2, a novel oncogene confers reoviral replication through Ras and p38 signaling pathway. Cancer Gene Ther. 2010 May;17(5):307-14 Nishino T, Takeuchi K, Gascoigne KE, Suzuki A, Hori T, Oyama T, Morikawa K, Cheeseman IM, Fukagawa T. CENP-TW-S-X forms a unique centromeric chromatin structure with a histone-like fold. Cell. 2012 Feb 3;148(3):487-501 Chun Y, Park B, Koh W, Lee S, Cheon Y, Kim R, Che L, Lee S. New centromeric component CENP-W is an RNAassociated nuclear matrix protein that interacts with nucleophosmin/B23 protein. J Biol Chem. 2011 Dec 9;286(49):42758-69 This article should be referenced as such: Kim HT, So JH, Jung SH, Ahn DG, Koh W, Kim NS, Kim SH, Lee S, Kim CH. Cug2 is essential for normal mitotic control and Atlas Genet Cytogenet Oncol Haematol. 2014; 18(1) Jeon S, Lee S. CENPW (centromere protein W). Atlas Genet Cytogenet Oncol Haematol. 2014; 18(1):5-7. 7