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Gene Section Mini Review Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Gene Section Mini Review MAP4 (microtubule-associated protein 4) Eva Maria Murga Penas, Judith Dierlamm Dept Oncology, Hematology, BMT with section Pneumology, Hubertus Wald Tumorzentrum - University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Martinistr 52, 20246 Hamburg, Germany (EMM, JD) Published in Atlas Database: June 2009 Online updated version : http://AtlasGeneticsOncology.org/Genes/MAP4ID44410ch3p21.html DOI: 10.4267/2042/44754 This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence. © 2010 Atlas of Genetics and Cytogenetics in Oncology and Haematology interaction with the promoter region of MAP4. Identity Overexpression of MAP4 markedly inhibits P53 Other names: MAP-4; MGC8617 mediated apoptosis (Murphy et al., 1996; Murphy et al., HGNC (Hugo): MAP4 1999). Location: 3p21.31 Transcription Centromere to telomere transcription. The multiple MAP4 isoforms are generated by alternative splicing (see figure below). Protein Description The protein encoded by the MAP4 gene is the major microtubule-associated protein in non-neuronal tissues and belongs to the group of microtubule-associated proteins (MAPs) of the MAP2/Tau family (Bulinski et al., 1980; Chapin et al., 1995). MAP4 contains a projection domain in its extreme N-terminus and a microtubule binding domain (MTB) in its carboxyl- terminal portion. The MTB domain consists of 3 MAP4 gene (3p21). FISH on normal lymphocytes using the subdomains, a Proline-rich region, a Repeat region BAC clone 395P16 on 3p21 obtained from the RPCI-11 library consisting of an Assembly-Promoting (AP) sequence of (Roswell Park Cancer Institute, Buffalo, NY). BAC 395P16 contains sequences derived immediately downstream of the 18-amino acids (Aas) residues, and a Tail region rich in MAP4 gene and is translocated to the partner chromosome in hydophobic and acidic Aas. Three to five repeats of the case of a translocation involving MAP4. AP sequence have been described in MAP4 (Aizawa et al., 1990). In vitro experiments with bovine MAP4 DNA/RNA have shown that the number of repeat sequences affects the microtubule surface properties (Tokuraku et al., Description 2003). MAP4 is encoded by a single-copy gene spanning a Expression region of ~238 kb of genomic DNA. Five alternative transcripts have been described (West et al., 1991). Widespread tissue distribution but absent from neurons MAP4 is down-regulated by P53 at the transcriptional (Bulinski and Borisy, 1980; Aizawa et al., 1990; level. The repression of MAP4 by P53 is exerted by Chapin and Bulinski, 1991; West et al., 1991). Atlas Genet Cytogenet Oncol Haematol. 2010; 14(5) 460 MAP4 (microtubule-associated protein 4) Murga Penas EM, Dierlamm J mRNA splice variants of MAP4. Nucleotide assignation according to GenBank sequence NT_022517 REGION: 47832180..48070769 GPS_000125239 (Homo sapiens chromosome 3 genomic contig, GRCh37 reference primary assembly). Schematic representation of the MAP4 protein. Localisation Implicated in Cytoplasmic. Diffuse large B-cell non-Hodgkin's Function lymphoma (DLBCL), centroblastic MAP4 binds to, polymerizes, and stabilizes subtype microtubules and is thought to regulate microtubule Disease dynamics during the cell cycle. In eukaryotic cells, the Non-reciprocal der(18)t(3;18)(p21;q21)/MALT1- onset of M phase is regulated by the p34cdc2/Cyclin B MAP4 translocation. complex, which controls changes in microtubule dynamic properties at the G2 to M phase transition of Cytogenetics the cell cycle The control of the microtubule Rearrangements of the MALT1 gene by the reorganization at mitosis is supposed to be directly translocations t(11;18)(q21;q21)/API2-MALT1 and regulated by phosphorylation of MAP4 by the p34cdc2 t(14;18)(q32;q21)/IGH-MALT1 are the most frequent kinase activity (Ookata et al., 1997). structural chromosomal abnormalities in MALT lymphomas and lead to an activation of the NF-kB Homology pathway (Dierlamm et al., 1999; Uren et al., 2000; About 80% similarity/70% identity among the human, Lucas et al., 2001; Streubel et al., 2003). In both mouse, and bovine Aas sequences (West et al., 1991). translocations the caspase-like domain of MALT1 is invariabily involved. Atlas Genet Cytogenet Oncol Haematol. 2010; 14(5) 461 MAP4 (microtubule-associated protein 4) Murga Penas EM, Dierlamm J Schematic representation of the localization of the breakpoints in MALT1 and MAP4 and the corresponding fusion product. Unlike the API2-MALT1 and IGH-MALT1 products, homologous to the microtubule-binding domains of neuronal the MALT1-MAP4 fusion product does not involve the MAP2 and tau. J Cell Sci. 1991 Jan;98 ( Pt 1):27-36 caspase-like domain, which is essential for activation of West RR, Tenbarge KM, Olmsted JB. A model for microtubule- NF-kB. The absence of the caspase like domain in the associated protein 4 structure. Domains defined by comparisons of human, mouse, and bovine sequences. J Biol MALT1-MAP4 fusion product distinguishes this novel Chem. 1991 Nov 15;266(32):21886-96 gene fusion, MALT1-MAP4, from the t(11;18)/API2- MALT1 and the t(14;18)/IGH-MALT1 and points to a Chapin SJ, Lue CM, Yu MT, Bulinski JC. Differential expression of alternatively spliced forms of MAP4: a repertoire new mechanism of deregulation of MALT1 (Murga of structurally different microtubule-binding domains. Penas et al., 2006). Biochemistry. 1995 Feb 21;34(7):2289-301 Hybrid/Mutated gene Murphy M, Hinman A, Levine AJ. Wild-type p53 negatively The 5'MALT1-3'MAP4 fusion product is the result of regulates the expression of a microtubule-associated protein. an unbalanced translocation that fuses "in frame" the Genes Dev. 1996 Dec 1;10(23):2971-80 exon 9 of MALT1 located on 18q21 to exon 9 of Ookata K, Hisanaga S, Sugita M, Okuyama A, Murofushi H, MAP4 located on 3p21 (Murga Penas et al., 2006). The Kitazawa H, Chari S, Bulinski JC, Kishimoto T. MAP4 is the in MALT1-MAP4 fusion is located on the derivative vivo substrate for CDC2 kinase in HeLa cells: identification of an M-phase specific and a cell cycle-independent chromosome 18 and due to a partial deletion of phosphorylation site in MAP4. Biochemistry. 1997 Dec MALT1 sequences telomeric to exon 9 the reciprocal 16;36(50):15873-83 transcript MAP4-MALT1 is absent. Dierlamm J, Baens M, Wlodarska I, Stefanova-Ouzounova M, The MALT1-MAP4 chimeric product corresponds to a Hernandez JM, Hossfeld DK, De Wolf-Peeters C, Hagemeijer fusion of the MALT1 gene at nucleotide 1276 A, Van den Berghe H, Marynen P. The apoptosis inhibitor gene (Genebank Accession No. NM_006785) to the MAP4 API2 and a novel 18q gene, MLT, are recurrently rearranged in the t(11;18)(q21;q21) associated with mucosa-associated gene at nucleotide 2469 (Genebank Accession No. lymphoid tissue lymphomas. Blood. 1999 Jun 1;93(11):3601-9 NM_002375). Murphy M, Ahn J, Walker KK, Hoffman WH, Evans RM, Levine AJ, George DL. Transcriptional repression by wild-type p53 References utilizes histone deacetylases, mediated by interaction with mSin3a. Genes Dev. 1999 Oct 1;13(19):2490-501 Bulinski JC, Borisy GG. Widespread distribution of a 210,000 mol wt microtubule-associated protein in cells and tissues of Uren AG, O'Rourke K, Aravind LA, Pisabarro MT, Seshagiri S, primates. J Cell Biol. 1980 Dec;87(3 Pt 1):802-8 Koonin EV, Dixit VM. Identification of paracaspases and metacaspases: two ancient families of caspase-like proteins, Aizawa H, Emori Y, Mori A, Murofushi H, Sakai H, Suzuki K. one of which plays a key role in MALT lymphoma. Mol Cell. Functional analyses of the domain structure of microtubule- 2000 Oct;6(4):961-7 associated protein-4 (MAP-U). J Biol Chem. 1991 May 25;266(15):9841-6 Lucas PC, Yonezumi M, Inohara N, McAllister-Lucas LM, Abazeed ME, Chen FF, Yamaoka S, Seto M, Nunez G. Bcl10 Chapin SJ, Bulinski JC. Non-neuronal 210 x 10(3) Mr and MALT1, independent targets of chromosomal translocation microtubule-associated protein (MAP4) contains a domain in malt lymphoma, cooperate in a novel NF-kappa B signaling pathway. J Biol Chem. 2001 Jun 1;276(22):19012-9 Atlas Genet Cytogenet Oncol Haematol. 2010; 14(5) 462 MAP4 (microtubule-associated protein 4) Murga Penas EM, Dierlamm J Streubel B, Lamprecht A, Dierlamm J, Cerroni L, Stolte M, Ott ML, Dierlamm J. A novel fusion of the MALT1 gene and the G, Raderer M, Chott A. T(14;18)(q32;q21) involving IGH and microtubule-associated protein 4 (MAP4) gene occurs in MALT1 is a frequent chromosomal aberration in MALT diffuse large B-cell lymphoma. Genes Chromosomes Cancer. lymphoma. Blood. 2003 Mar 15;101(6):2335-9 2006 Sep;45(9):863-73 Tokuraku K, Matsushima K, Matui T, Nakagawa H, Katsuki M, This article should be referenced as such: Majima R, Kotani S. The number of repeat sequences in microtubule-associated protein 4 affects the microtubule Murga Penas EM, Dierlamm J. MAP4 (microtubule-associated surface properties. J Biol Chem. 2003 Aug 8;278(32):29609-18 protein 4). Atlas Genet Cytogenet Oncol Haematol. 2010; 14(5):460-463. Murga Penas EM, Kawadler H, Siebert R, Frank M, Ye H, Hinz K, Becher C, Hummel M, Barth TF, Bokemeyer C, Stein H, Trümper L, Möller P, Marynen P, Du MQ, Yang X, Hansmann Atlas Genet Cytogenet Oncol Haematol. 2010; 14(5) 463 .
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