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Open Access 01-12-2014

Towards an understanding of the structure and function of MTA1

Authors: Christopher J. Millard, Louise Fairall, John W. R. Schwabe

Published in: Cancer and Metastasis Reviews | Issue 4/2014

Abstract

Gene expression is controlled through the recruitment of large coregulator complexes to specific gene loci to regulate chromatin structure by modifying epigenetic marks on DNA and histones. Metastasis-associated protein 1 (MTA1) is an essential component of the nucleosome remodelling and deacetylase (NuRD) complex that acts as a scaffold protein to assemble enzymatic activity and nucleosome targeting proteins. MTA1 consists of four characterised domains, a number of interaction motifs, and regions that are predicted to be intrinsically disordered. The ELM2-SANT domain is one of the best-characterised regions of MTA1, which recruits histone deacetylase 1 (HDAC1) and activates the enzyme in the presence of inositol phosphate. MTA1 is highly upregulated in several types of aggressive tumours and is therefore a possible target for cancer therapy. In this review, we summarise the structure and function of the four domains of MTA1 and discuss the possible functions of less well-characterised regions of the protein.

Xue, Y., Wong, J., Moreno, G. T., Young, M. K., Côté, J., & Wang, W. (1998). NURD, a novel complex with both ATP-dependent chromatin-remodeling and histone deacetylase activities. Molecular Cell, 2(6), 851–861.PubMedCrossRef

Zhang, Y., Ng, H.-H., Erdjument-Bromage, H., Tempst, P., Bird, A., & Reinberg, D. (1999). Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation. Genes and Development, 13(15), 1924–1935.PubMedCentralPubMedCrossRef

Humphrey, G. W., Wang, Y., Russanova, V. R., Hirai, T., Qin, J., Nakatani, Y., & Howard, B. H. (2001). Stable histone deacetylase complexes distinguished by the presence of SANT domain proteins CoREST/kiaa0071 and Mta-L1. Journal of Biological Chemistry, 276(9), 6817–6824. doi:10.1074/jbc.M007372200.PubMedCrossRef

Wen, Y. D., Perissi, V., Staszewski, L. M., Yang, W. M., Krones, A., Glass, C. K., et al. (2000). The histone deacetylase-3 complex contains nuclear receptor corepressors. Proceedings of the National Academy of Sciences of the United States of America, 97(13), 7202–7207.PubMedCentralPubMedCrossRef

Laherty, C. D., Yang, W. M., Sun, J. M., Davie, J. R., Seto, E., & Eisenman, R. N. (1997). Histone deacetylases associated with the mSin3 corepressor mediate mad transcriptional repression. Cell, 89(3), 349–356.PubMedCrossRef

Bantscheff, M., Hopf, C., Savitski, M. M., Dittmann, A., Grandi, P., Michon, A.-M., et al. (2011). Chemoproteomics profiling of HDAC inhibitors reveals selective targeting of HDAC complexes. Nature Biotechnology, 29(3), 255–265. doi:10.1038/nbt.1759.PubMedCrossRef

Guenther, M. G., Lane, W. S., Fischle, W., Verdin, E., Lazar, M. A., & Shiekhattar, R. (2000). A core SMRT corepressor complex containing HDAC3 and TBL1, a WD40-repeat protein linked to deafness. Genes and Development, 14(9), 1048–1057.PubMedCentralPubMed

Manavathi, B., & Kumar, R. (2007). Metastasis tumor antigens, an emerging family of multifaceted master coregulators. Journal of Biological Chemistry, 282(3), 1529–1533. doi:10.1074/jbc.R600029200.PubMedCrossRef

Denslow, S. A., & Wade, P. A. (2007). The human Mi-2/NuRD complex and gene regulation. Oncogene, 26(37), 5433–5438. doi:10.1038/sj.onc.1210611.PubMedCrossRef

10.

Allen, H. F., Wade, P. A., & Kutateladze, T. G. (2013). The NuRD architecture. Cellular and Molecular Life Sciences, 70(19), 3513–3524. doi:10.1007/s00018-012-1256-2.PubMedCentralPubMedCrossRef

11.

Toh, Y., Pencil, S. D., & Nicolson, G. L. (1994). A novel candidate metastasis-associated gene, mta1, differentially expressed in highly metastatic mammary adenocarcinoma cell lines. cDNA cloning, expression, and protein analyses. Journal of Biological Chemistry, 269(37), 22958–22963.PubMed

12.

Toh, Y., & Nicolson, G. L. (2009). The role of the MTA family and their encoded proteins in human cancers: molecular functions and clinical implications. Clinical and Experimental Metastasis, 26(3), 215–227. doi:10.1007/s10585-008-9233-8.PubMedCrossRef

13.

Lai, A. Y., & Wade, P. A. (2011). Cancer biology and NuRD: a multifaceted chromatin remodelling complex. Nature Reviews. Cancer, 11(8), 588–596. doi:10.1038/nrc3091.PubMedCentralPubMedCrossRef

14.

Zhang, H., Stephens, L. C., & Kumar, R. (2006). Metastasis tumor antigen family proteins during breast cancer progression and metastasis in a reliable mouse model for human breast cancer. Clinical Cancer Research an Official Journal of the American Association for Cancer Research, 12(5), 1479–1486. doi:10.1158/1078-0432.CCR-05-1519.PubMedCrossRef

15.

Prisco, M. G., Zannoni, G. F., De Stefano, I., Vellone, V. G., Tortorella, L., Fagotti, A., et al. (2012). Prognostic role of metastasis tumor antigen 1 in patients with ovarian cancer: a clinical study. Human Pathology, 43(2), 282–288. doi:10.1016/j.humpath.2011.05.002.PubMedCrossRef

16.

Balasenthil, S., Broaddus, R. R., & Kumar, R. (2006). Expression of metastasis-associated protein 1 (MTA1) in benign endometrium and endometrial adenocarcinomas. Human Pathology, 37(6), 656–661. doi:10.1016/j.humpath.2006.01.024.PubMedCrossRef

17.

Filippakopoulos, P., & Knapp, S. (2012). The bromodomain interaction module. FEBS Letters, 586(17), 2692–2704. doi:10.1016/j.febslet.2012.04.045.PubMedCrossRef

18.

Wade, P. A., Jones, P. L., Vermaak, D., & Wolffe, A. P. (1998). A multiple subunit Mi-2 histone deacetylase from Xenopus laevis cofractionates with an associated Snf2 superfamily ATPase. Current Biology, 8(14), 843–846.PubMedCrossRef

19.

Bouazoune, K., Mitterweger, A., Längst, G., Imhof, A., Akhtar, A., Becker, P. B., & Brehm, A. (2002). The dMi-2 chromodomains are DNA binding modules important for ATP-dependent nucleosome mobilization. EMBO Journal, 21(10), 2430–2440. doi:10.1093/emboj/21.10.2430.PubMedCentralPubMedCrossRef

20.

Murzina, N. V., Pei, X.-Y., Zhang, W., Sparkes, M., Vicente-Garcia, J., Pratap, J. V., et al. (2008). Structural basis for the recognition of histone H4 by the histone-chaperone RbAp46. Structure, 16(7), 1077–1085. doi:10.1016/j.str.2008.05.006.PubMedCentralPubMedCrossRef

21.

Brackertz, M., Gong, Z., Leers, J., & Renkawitz, R. (2006). p66alpha and p66beta of the Mi-2/NuRD complex mediate MBD2 and histone interaction. Nucleic Acids Research, 34(2), 397–406. doi:10.1093/nar/gkj437.PubMedCentralPubMedCrossRef

22.

Baubec, T., Ivánek, R., Lienert, F., & Schübeler, D. (2013). Methylation-dependent and -independent genomic targeting principles of the MBD protein family. Cell, 153(2), 480–492. doi:10.1016/j.cell.2013.03.011.PubMedCrossRef

23.

Zhang, Y., LeRoy, G., Seelig, H. P., Lane, W. S., & Reinberg, D. (1998). The dermatomyositis-specific autoantigen Mi2 is a component of a complex containing histone deacetylase and nucleosome remodeling activities. Cell, 95(2), 279–289.PubMedCrossRef

24.

Toh, Y., Kuninaka, S., Endo, K., Oshiro, T., Ikeda, Y., Nakashima, H., et al. (2000). Molecular analysis of a candidate metastasis-associated gene, MTA1: possible interaction with histone deacetylase 1. Journal of Experimental and Clinical Cancer Research, 19(1), 105–111.PubMed

25.

Alqarni, S. S. M., Murthy, A., Zhang, W., Przewloka, M. R., Silva, A. P. G., Watson, A. A., et al. (2014). Insight into the architecture of the NuRD complex: Structure of the RbAp48-MTA1 sub-complex. Journal of Biological Chemistry, 289(32), 21844–21855. doi:10.1074/jbc.M114.558940.PubMedCentralPubMedCrossRef

26.

Millard, C. J., Watson, P. J., Celardo, I., Gordiyenko, Y., Cowley, S. M., Robinson, C. V., et al. (2013). Class I HDACs share a common mechanism of regulation by inositol phosphates. Molecular Cell, 51(1), 57–67. doi:10.1016/j.molcel.2013.05.020.PubMedCentralPubMedCrossRef

27.

Nair, S. S., Li, D.-Q., & Kumar, R. (2013). A core chromatin remodeling factor instructs global chromatin signaling through multivalent reading of nucleosome codes. Molecular Cell, 49(4), 704–718. doi:10.1016/j.molcel.2012.12.016.PubMedCentralPubMedCrossRef

28.

Yaguchi, M., Wada, Y., Toh, Y., Iguchi, H., Kono, A., Matsusue, K., & Takiguchi, S. (2005). Identification and characterization of the variants of metastasis-associated protein 1 generated following alternative splicing. Biochimica et Biophysica Acta, 1732(1–3), 8–14. doi:10.1016/j.bbaexp.2005.12.001.PubMedCrossRef

29.

Kumar, R., Wang, R.-A., Mazumdar, A., Talukder, A. H., Mandal, M., Yang, Z., et al. (2002). A naturally occurring MTA1 variant sequesters oestrogen receptor-alpha in the cytoplasm. Nature, 418(6898), 654–657. doi:10.1038/nature00889.PubMedCrossRef

30.

Kleene, R., Zdzieblo, J., Wege, K., & Kern, H. F. (1999). A novel zymogen granule protein (ZG29p) and the nuclear protein MTA1p are differentially expressed by alternative transcription initiation in pancreatic acinar cells of the rat. Journal of Cell Science, 112(Pt 15), 2539–2548.PubMed

31.

Nawa, A., Nishimori, K., Lin, P., Maki, Y., Moue, K., Sawada, H., et al. (2000). Tumor metastasis-associated human MTA1 gene: its deduced protein sequence, localization, and association with breast cancer cell proliferation using antisense phosphorothioate oligonucleotides. Journal of Cellular Biochemistry, 79(2), 202–212.PubMedCrossRef

32.

Solari, F., Bateman, A., & Ahringer, J. (1999). The Caenorhabditis elegans genes egl-27 and egr-1 are similar to MTA1, a member of a chromatin regulatory complex, and are redundantly required for embryonic patterning. Development, 126(11), 2483–2494.PubMed

33.

Nicolson, G. L., Nawa, A., Toh, Y., Taniguchi, S., Nishimori, K., & Moustafa, A. (2003). Tumor metastasis-associated human MTA1 gene and its MTA1 protein product: role in epithelial cancer cell invasion, proliferation and nuclear regulation. Clinical and Experimental Metastasis, 20(1), 19–24.PubMedCrossRef

34.

Boyer, L. A., Latek, R. R., & Peterson, C. L. (2004). The SANT domain: a unique histone-tail-binding module? Nature Reviews Molecular Cell Biology, 5(2), 158–163. doi:10.1038/nrm1314.PubMedCrossRef

35.

Aasland, R., Stewart, A. F., & Gibson, T. (1996). The SANT domain: a putative DNA-binding domain in the SWI-SNF and ADA complexes, the transcriptional co-repressor N-CoR and TFIIIB. Trends in Biochemical Sciences, 21(3), 87–88.PubMed

36.

Ogata, K., Morikawa, S., Nakamura, H., Sekikawa, A., Inoue, T., Kanai, H., et al. (1994). Solution structure of a specific DNA complex of the Myb DNA-binding domain with cooperative recognition helices. Cell, 79(4), 639–648.PubMedCrossRef

37.

Guenther, M. G., Barak, O., & Lazar, M. A. (2001). The SMRT and N-CoR corepressors are activating cofactors for histone deacetylase 3. Molecular and Cellular Biology, 21(18), 6091–6101.PubMedCentralPubMedCrossRef

38.

Watson, P. J., Fairall, L., Santos, G. M., & Schwabe, J. W. R. (2012). Structure of HDAC3 bound to co-repressor and inositol tetraphosphate. Nature, 481(7381), 335–340. doi:10.1038/nature10728.PubMedCentralPubMed

39.

Barker, C. J., Wright, J., Hughes, P. J., Kirk, C. J., & Michell, R. H. (2004). Complex changes in cellular inositol phosphate complement accompany transit through the cell cycle. Biochemical Journal, 380(Pt 2), 465–473. doi:10.1042/BJ20031872.PubMedCentralPubMedCrossRef

40.

Zhang, Y., Sun, Z. W., Iratni, R., Erdjument-Bromage, H., Tempst, P., Hampsey, M., & Reinberg, D. (1998). SAP30, a novel protein conserved between human and yeast, is a component of a histone deacetylase complex. Molecular Cell, 1(7), 1021–1031.PubMedCrossRef

41.

Kuzmichev, A., Nishioka, K., Erdjument-Bromage, H., Tempst, P., & Reinberg, D. (2002). Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein. Genes and Development, 16(22), 2893–2905. doi:10.1101/gad.1035902.PubMedCentralPubMedCrossRef

42.

Barak, O., Lazzaro, M. A., Lane, W. S., Speicher, D. W., Picketts, D. J., & Shiekhattar, R. (2003). Isolation of human NURF: a regulator of Engrailed gene expression. EMBO Journal, 22(22), 6089–6100. doi:10.1093/emboj/cdg582.PubMedCentralPubMedCrossRef

43.

Schmitges, F. W., Prusty, A. B., Faty, M., Stützer, A., Lingaraju, G. M., Aiwazian, J., et al. (2011). Histone methylation by PRC2 is inhibited by active chromatin marks. Molecular Cell, 42(3), 330–341. doi:10.1016/j.molcel.2011.03.025.PubMedCrossRef

44.

Lejon, S., Thong, S. Y., Murthy, A., AlQarni, S., Murzina, N. V., Blobel, G. A., et al. (2011). Insights into association of the NuRD complex with FOG-1 from the crystal structure of an RbAp48 FOG-1 complex. Journal of Biological Chemistry, 286(2), 1196–1203. doi:10.1074/jbc.M110.195842.PubMedCentralPubMedCrossRef

45.

Roche, A. E., Bassett, B. J., Samant, S. A., Hong, W., Blobel, G. A., & Svensson, E. C. (2008). The zinc finger and C-terminal domains of MTA proteins are required for FOG-2-mediated transcriptional repression via the NuRD complex. Journal of Molecular and Cellular Cardiology, 44(2), 352–360. doi:10.1016/j.yjmcc.2007.10.023.PubMedCentralPubMedCrossRef

46.

Fu, J., Qin, L., He, T., Qin, J., Hong, J., Wong, J., et al. (2011). The TWIST/Mi2/NuRD protein complex and its essential role in cancer metastasis. Cell Research, 21(2), 275–289. doi:10.1038/cr.2010.118.PubMedCentralPubMedCrossRef

47.

Callebaut, I., Courvalin, J. C., & Mornon, J. P. (1999). The BAH (bromo-adjacent homology) domain: a link between DNA methylation, replication and transcriptional regulation. FEBS Letters, 446(1), 189–193.PubMedCrossRef

48.

Nicolas, R. H., & Goodwin, G. H. (1996). Molecular cloning of polybromo, a nuclear protein containing multiple domains including five bromodomains, a truncated HMG-box, and two repeats of a novel domain. Gene, 175(1–2), 233–240.PubMedCrossRef

49.

Oliver, A. W., Jones, S. A., Roe, S. M., Matthews, S., Goodwin, G. H., & Pearl, L. H. (2005). Crystal structure of the proximal BAH domain of the polybromo protein. Biochemical Journal, 389(Pt 3), 657–664. doi:10.1042/BJ20050310.PubMedCentralPubMed

50.

Chambers, A. L., Pearl, L. H., Oliver, A. W., & Downs, J. A. (2013). The BAH domain of Rsc2 is a histone H3 binding domain. Nucleic Acids Research, 41(19), 9168–9182. doi:10.1093/nar/gkt662.PubMedCentralPubMedCrossRef

51.

Armache, K.-J., Garlick, J. D., Canzio, D., Narlikar, G. J., & Kingston, R. E. (2011). Structural basis of silencing: Sir3 BAH domain in complex with a nucleosome at 3.0 Å resolution. Science, 334(6058), 977–982. doi:10.1126/science.1210915.PubMedCentralPubMedCrossRef

52.

Wang, F., Li, G., Altaf, M., Lu, C., Currie, M. A., Johnson, A., & Moazed, D. (2013). Heterochromatin protein Sir3 induces contacts between the amino terminus of histone H4 and nucleosomal DNA. Proceedings of the National Academy of Sciences of the United States of America, 110(21), 8495–8500. doi:10.1073/pnas.1300126110.PubMedCentralPubMedCrossRef

53.

Arnaudo, N., Fernández, I. S., McLaughlin, S. H., Peak-Chew, S. Y., Rhodes, D., & Martino, F. (2013). The N-terminal acetylation of Sir3 stabilizes its binding to the nucleosome core particle. Nature Structural & Molecular Biology, 20(9), 1119–1121. doi:10.1038/nsmb.2641.CrossRef

54.

Yang, D., Fang, Q., Wang, M., Ren, R., Wang, H., He, M., et al. (2013). Nα-acetylated Sir3 stabilizes the conformation of a nucleosome-binding loop in the BAH domain. Nature Structural and Molecular Biology, 20(9), 1116–1118. doi:10.1038/nsmb.2637.PubMedCrossRef

55.

Kuo, A. J., Song, J., Cheung, P., Ishibe-Murakami, S., Yamazoe, S., Chen, J. K., et al. (2012). The BAH domain of ORC1 links H4K20me2 to DNA replication licensing and Meier-Gorlin syndrome. Nature, 484(7392), 115–119. doi:10.1038/nature10956.PubMedCentralPubMedCrossRef

56.

Song, J., Rechkoblit, O., Bestor, T. H., & Patel, D. J. (2011). Structure of DNMT1-DNA complex reveals a role for autoinhibition in maintenance DNA methylation. Science, 331(6020), 1036–1040. doi:10.1126/science.1195380.PubMedCrossRef

57.

Zheng, R., & Blobel, G. A. (2010). GATA transcription factors and cancer. Genes & Cancer, 1(12), 1178–1188. doi:10.1177/1947601911404223.CrossRef

58.

Omichinski, J. G., Clore, G. M., Schaad, O., Felsenfeld, G., Trainor, C., Appella, E., et al. (1993). NMR structure of a specific DNA complex of Zn-containing DNA binding domain of GATA-1. Science, 261(5120), 438–446.PubMedCrossRef

59.

Ren, R., Mayer, B. J., Cicchetti, P., & Baltimore, D. (1993). Identification of a ten-amino acid proline-rich SH3 binding site. Science, 259(5098), 1157–1161.PubMedCrossRef

60.

Yu, H., Chen, J. K., Feng, S., Dalgarno, D. C., Brauer, A. W., & Schreiber, S. L. (1994). Structural basis for the binding of proline-rich peptides to SH3 domains. Cell, 76(5), 933–945.PubMedCrossRef

61.

Rigbolt, K. T. G., Prokhorova, T. A., Akimov, V., Henningsen, J., Johansen, P. T., Kratchmarova, I., et al. (2011). System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Science Signaling, 4(164), rs3. doi:10.1126/scisignal.2001570.PubMedCrossRef

62.

Mishra, S. K., Yang, Z., Mazumdar, A., Talukder, A. H., Larose, L., & Kumar, R. (2004). Metastatic tumor antigen 1 short form (MTA1s) associates with casein kinase I-gamma2, an estrogen-responsive kinase. Oncogene, 23(25), 4422–4429. doi:10.1038/sj.onc.1207569.PubMedCrossRef

63.

Toh, Y., Pencil, S. D., & Nicolson, G. L. (1995). Analysis of the complete sequence of the novel metastasis-associated candidate gene, mta1, differentially expressed in mammary adenocarcinoma and breast cancer cell lines. Gene, 159(1), 97–104.PubMedCrossRef

64.

Zhang, J., Kalkum, M., Chait, B. T., & Roeder, R. G. (2002). The N-CoR-HDAC3 nuclear receptor corepressor complex inhibits the JNK pathway through the integral subunit GPS2. Molecular Cell, 9(3), 611–623.PubMedCrossRef

65.

McGuffin, L. J., Bryson, K., & Jones, D. T. (2000). The PSIPRED protein structure prediction server. Bioinformatics, 16(4), 404–405.PubMedCrossRef

66.

Ward, J. J., McGuffin, L. J., Bryson, K., Buxton, B. F., & Jones, D. T. (2004). The DISOPRED server for the prediction of protein disorder. Bioinformatics, 20(13), 2138–2139. doi:10.1093/bioinformatics/bth195.PubMedCrossRef

Title: Towards an understanding of the structure and function of MTA1
Authors: Christopher J. Millard
Louise Fairall
John W. R. Schwabe
Publication date: 01-12-2014
Publisher: Springer US
Published in: Cancer and Metastasis Reviews / Issue 4/2014
Print ISSN: 0167-7659
Electronic ISSN: 1573-7233
DOI: https://doi.org/10.1007/s10555-014-9513-5

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