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{{About|proteins|the Islamic TV channel|MTA 1}}
{{Infobox_gene}}
'''Metastasis-associated protein MTA1''' is a [[protein]] that in humans is encoded by the ''MTA1'' [[gene]].  MTA1 is the founding member of the MTA family of genes.<ref name="1-Toh">{{cite journal | vauthors = Toh Y, Pencil SD, Nicolson GL | title = A novel candidate metastasis-associated gene, mta1, differentially expressed in highly metastatic mammary adenocarcinoma cell lines. cDNA cloning, expression, and protein analyses | journal = The Journal of Biological Chemistry | volume = 269 | issue = 37 | pages = 22958–63 | date = Sep 1994 | pmid = 8083195 }}</ref><ref name="2-toh">{{cite journal | vauthors = Toh Y, Nicolson GL | title = Properties and clinical relevance of MTA1 protein in human cancer | journal = Cancer Metastasis Reviews | volume = 33 | issue = 4 | pages = 891–900 | date = Dec 2014 | pmid = 25359582 | doi = 10.1007/s10555-014-9516-2 }}</ref> MTA1 is primarily localized in the nucleus but also found to be distributed in the extra-nuclear compartments.<ref name="3-liu">{{cite journal | vauthors = Liu J, Xu D, Wang H, Zhang Y, Chang Y, Zhang J, Wang J, Li C, Liu H, Zhao M, Lin C, Zhan Q, Huang C, Qian H | title = The subcellular distribution and function of MTA1 in cancer differentiation | journal = Oncotarget | volume = 5 | issue = 13 | pages = 5153–64 | date = Jul 2014 | pmid = 24970816 | doi = 10.18632/oncotarget.2095 | pmc=4148129}}</ref><ref name="4-Liu">{{cite journal | vauthors = Liu J, Wang H, Huang C, Qian H | title = Subcellular localization of MTA proteins in normal and cancer cells | journal = Cancer Metastasis Reviews | volume = 33 | issue = 4 | pages = 843–56 | date = Dec 2014 | pmid = 25398252 | doi = 10.1007/s10555-014-9511-7 }}</ref> MTA1 is a component of several chromatin remodeling complexes including the nucleosome remodeling and deacetylation complex ([[NuRD]]).<ref name="5-xue">{{cite journal | vauthors = Xue Y, Wong J, Moreno GT, Young MK, Côté J, Wang W | title = NURD, a novel complex with both ATP-dependent chromatin-remodeling and histone deacetylase activities | journal = Molecular Cell | volume = 2 | issue = 6 | pages = 851–61 | date = Dec 1998 | pmid = 9885572 | doi=10.1016/s1097-2765(00)80299-3}}</ref><ref name="6-Li">{{cite journal | vauthors = Li DQ, Kumar R | title = Unravelling the Complexity and Functions of MTA Coregulators in Human Cancer | journal = Advances in Cancer Research | volume = 127 | pages = 1–47 | date = 2015 | pmid = 26093897 | doi = 10.1016/bs.acr.2015.04.005 }}</ref> MTA1 regulates gene expression by functioning as a coregulator to integrate DNA-interacting factors to gene activity.<ref name="7-Kumar">{{cite book | editor-last1 = O'Malley | editor-first1 = Bert W. | editor-last2 = Kumar | editor-first2 = Rakesh | name-list-format = vanc | title = Nuclear Receptor Coregulators and Human Diseases | date = 2008 | publisher = World Scientific | location = Hackensack, N.J. | isbn = 978-981-281-917-8 | pages = 195–218 | chapter = Coregulators as Oncogenes and Tumor Suppressors | first1 = Rakesh | last1 = Kumar | first2 = Anupama E.| last2 =  Gururaj | doi = 10.1142/9789812819178_0004 }}</ref> MTA1 participates in physiological functions in the normal and cancer cells.<ref name="8-sen">{{cite journal | vauthors = Sen N, Gui B, Kumar R | title = Physiological functions of MTA family of proteins | journal = Cancer Metastasis Reviews | volume = 33 | issue = 4 | pages = 869–77 | date = Dec 2014 | pmid = 25344801 | doi = 10.1007/s10555-014-9514-4 | pmc=4245464}}</ref><ref name="9-sen">{{cite journal | vauthors = Sen N, Gui B, Kumar R | title = Role of MTA1 in cancer progression and metastasis | journal = Cancer Metastasis Reviews | volume = 33 | issue = 4 | pages = 879–89 | date = Dec 2014 | pmid = 25344802 | doi = 10.1007/s10555-014-9515-3 | pmc=4245458}}</ref> MTA1 is one of the most upregulated proteins in human cancer and associates with cancer progression, aggressive phenotypes, and poor prognosis of cancer patients.<ref name="6-Li" /><ref name="10-kumar">{{cite journal | vauthors = Kumar R | title = Functions and clinical relevance of MTA proteins in human cancer. Preface | journal = Cancer Metastasis Reviews | volume = 33 | issue = 4 | pages = 835 | date = Dec 2014 | pmid = 25348751 | doi = 10.1007/s10555-014-9509-1 | pmc=4245326}}</ref>

== Discovery ==

''MTA1'' was first cloned by Toh, Pencil and Nicholson in 1994 as a differentially expressed gene in a highly metastatic rat breast cancer cell line.<ref name="1-Toh" /><ref name="2-toh" /> The role in MTA1 in chromatin remodeling was deduced due to the presence of MTA1 polypeptides in the NuRD complex.<ref name="5-xue" /> The first direct target of the MTA1-NuRD complex was ERα.<ref name="11-mazumdar">{{cite journal | vauthors = Mazumdar A, Wang RA, Mishra SK, Adam L, Bagheri-Yarmand R, Mandal M, Vadlamudi RK, Kumar R | title = Transcriptional repression of oestrogen receptor by metastasis-associated protein 1 corepressor | journal = Nature Cell Biology | volume = 3 | issue = 1 | pages = 30–7 | date = Jan 2001 | pmid = 11146623 | doi = 10.1038/35050532 }}</ref>

== Gene and spliced variants  ==

The MTA1 is 715/703 amino acids long, coded by one of three genes of the MTA family and localized on chromosome 14q32 in human and on chromosome 12F in mouse. There are 21 exons spread over a region of about 51-kb in human ''MTA1''.  Alternative splicing from 21 exons generates 20 transcripts, ranging from 416-bp to 2.9-kb long.<ref name="12-Kumar">{{cite journal | vauthors = Kumar R, Wang RA | title = Structure, expression and functions of MTA genes | journal = Gene | volume = 582 | issue = 2 | pages = 112–21 | date = May 2016 | pmid = 26869315 | doi = 10.1016/j.gene.2016.02.012 }}</ref> However, open-reading frames are present only in eight spliced transcripts which code six proteins and two polypeptides and remaining transcripts are non-coding long RNAs some of which retain intron sequences. Murine ''Mta1'' contains three protein coding transcripts and three non-coding RNA transcripts.<ref name="12-Kumar" /> Among human MTA1 variants, only two spliced variants are characterized: ZG29p variant is derived from the c-terminal ''MTA1'', with 251 amino acids and 29-kDa molecular weight;<ref name="13-kleen">{{cite journal | vauthors = Kleene R, Zdzieblo J, Wege K, Kern HF | title = 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 = Journal of Cell Science | volume = 112 | pages = 2539–48 | date = Aug 1999 | pmid = 10393810 | issue=15}}</ref> and MTA1s variant generated from alternative splicing of a middle exon followed by a frame-shift, is 430 amino acids and 47-kDa molecular weight.<ref name="14-kumar">{{cite journal | vauthors = Kumar R, Wang RA, Mazumdar A, Talukder AH, Mandal M, Yang Z, Bagheri-Yarmand R, Sahin A, Hortobagyi G, Adam L, Barnes CJ, Vadlamudi RK | title = A naturally occurring MTA1 variant sequesters oestrogen receptor-alpha in the cytoplasm | journal = Nature | volume = 418 | issue = 6898 | pages = 654–7 | date = Aug 2002 | pmid = 12167865 | doi = 10.1038/nature00889 }}</ref>

== Protein domains ==

The conserved domains of MTA1 include a BAH (Bromo-Adjacent Homology), a ELM2 (egl-27 and MTA1 homology), a SANT (SWI, ADA2, N-CoR, TFIIIB-B) and a GATA-like zinc finger. The C-terminal divergent region of MTA1 has an Src homology 3-binding domain, acidic regions, and nuclear localization signals. The presence of these domains revealed the role of MTA1 in interactions with modified or unmodified histone and non-histone proteins, chromatin remodeling, and modulation of gene transcription.<ref name="6-Li" /><ref name="15-mil">{{cite journal | vauthors = Millard CJ, Watson PJ, Celardo I, Gordiyenko Y, Cowley SM, Robinson CV, Fairall L, Schwabe JW | title = Class I HDACs share a common mechanism of regulation by inositol phosphates | journal = Molecular Cell | volume = 51 | issue = 1 | pages = 57–67 | date = Jul 2013 | pmid = 23791785 | doi = 10.1016/j.molcel.2013.05.020 | pmc=3710971}}</ref><ref name="16-alq">{{cite journal | vauthors = Alqarni SS, Murthy A, Zhang W, Przewloka MR, Silva AP, Watson AA, Lejon S, Pei XY, Smits AH, Kloet SL, Wang H, Shepherd NE, Stokes PH, Blobel GA, Vermeulen M, Glover DM, Mackay JP, Laue ED | title = Insight into the architecture of the NuRD complex: structure of the RbAp48-MTA1 subcomplex | journal = The Journal of Biological Chemistry | volume = 289 | issue = 32 | pages = 21844–55 | date = Aug 2014 | pmid = 24920672 | doi = 10.1074/jbc.M114.558940 | pmc=4139204}}</ref><ref name="17-mil">{{cite journal | vauthors = Millard CJ, Fairall L, Schwabe JW | title = Towards an understanding of the structure and function of MTA1 | journal = Cancer Metastasis Reviews | volume = 33 | issue = 4 | pages = 857–67 | date = Dec 2014 | pmid = 25352341 | doi = 10.1007/s10555-014-9513-5 | pmc=4244562}}</ref> MTA1 undergoes multiple post-translation modifications: acetylation on lysine 626, ubiquitination on lysine 182 and lysine 626, sumoylation on lysine 509, and methylation on lysine 532.<ref name="19-Ohshiro">{{cite journal | vauthors = Ohshiro K, Rayala SK, Wigerup C, Pakala SB, Natha RS, Gururaj AE, Molli PR, Månsson SS, Ramezani A, Hawley RG, Landberg G, Lee NH, Kumar R | title = Acetylation-dependent oncogenic activity of metastasis-associated protein 1 co-regulator | journal = EMBO Reports | volume = 11 | issue = 9 | pages = 691–7 | date = Sep 2010 | pmid = 20651739 | doi = 10.1038/embor.2010.99 | pmc=2933879}}</ref><ref name="19-Ohshiro"/><ref name="20-Sumo">{{cite journal | vauthors = Cong L, Pakala SB, Ohshiro K, Li DQ, Kumar R | title = SUMOylation and SUMO-interacting motif (SIM) of metastasis tumor antigen 1 (MTA1) synergistically regulate its transcriptional repressor function | journal = The Journal of Biological Chemistry | volume = 286 | issue = 51 | pages = 43793–808 | date = Dec 2011 | pmid = 21965678 | doi = 10.1074/jbc.M111.267237 | pmc=3243521}}</ref><ref name="21-Nair">{{cite journal | vauthors = Nair SS, Li DQ, Kumar R | title = A core chromatin remodeling factor instructs global chromatin signaling through multivalent reading of nucleosome codes | journal = Molecular Cell | volume = 49 | issue = 4 | pages = 704–18 | date = Feb 2013 | pmid = 23352453 | doi = 10.1016/j.molcel.2012.12.016 | pmc=3582764}}</ref> The structural insights of MTA1 domains are deduced from studies involving complexes with HDAC1 or RbAp48 subunits of the NuRD complexes.<ref name="15-mil" /><ref name="16-alq" /> The MTA1s variant is an N-terminal portion of MTA1 without nuclear localization sequence but contains a novel sequence of 33 amino acids in its C-terminal region. The novel sequence harbors a nuclear receptor binding motif LXXLL which confers MTA1 with an ability to interact with estrogen receptor alpha or other type I nuclear receptors.<ref name="14-kumar" /> The ZG29p variant represents the c-terminal MTA1 with two proline-rich SH3 binding sites.<ref name="13-kleen" /><ref name="22-kleen">{{cite journal | vauthors = Kleene R, Classen B, Zdzieblo J, Schrader M | title = SH3 binding sites of ZG29p mediate an interaction with amylase and are involved in condensation-sorting in the exocrine rat pancreas | journal = Biochemistry | volume = 39 | issue = 32 | pages = 9893–900 | date = Aug 2000 | pmid = 10933808 | doi=10.1021/bi000876i}}</ref>

== Regulation ==

Expression of MTA1 is influenced by transcription and non-transcriptional mechanisms. MTA1 expression is regulated by growth factors, growth factor receptors, oncogenes, environmental stress, ionizing radiation, inflammation, and hypoxia.<ref name="6-Li"/><ref name="9-sen"/> The transcription of ''MTA1'' is stimulated by transcriptional factors including, c-Myc,<ref name="23-zhang">{{cite journal | vauthors = Zhang XY, DeSalle LM, Patel JH, Capobianco AJ, Yu D, Thomas-Tikhonenko A, McMahon SB | title = Metastasis-associated protein 1 (MTA1) is an essential downstream effector of the c-MYC oncoprotein | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 102 | issue = 39 | pages = 13968–73 | date = Sep 2005 | pmid = 16172399 | doi = 10.1073/pnas.0502330102 | pmc=1236531}}</ref> SP1,<ref name="24-Li">{{cite journal | vauthors = Li DQ, Pakala SB, Reddy SD, Ohshiro K, Zhang JX, Wang L, Zhang Y, Moreno de Alborán I, Pillai MR, Eswaran J, Kumar R | title = Bidirectional autoregulatory mechanism of metastasis-associated protein 1-alternative reading frame pathway in oncogenesis | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 108 | issue = 21 | pages = 8791–6 | date = May 2011 | pmid = 21555589 | doi = 10.1073/pnas.1018389108 | pmc=3102345}}</ref> CUTL1 homeodomain,<ref name="25-Pakala">{{cite journal | vauthors = Pakala SB, Singh K, Reddy SD, Ohshiro K, Li DQ, Mishra L, Kumar R | title = TGF-β1 signaling targets metastasis-associated protein 1, a new effector in epithelial cells | journal = Oncogene | volume = 30 | issue = 19 | pages = 2230–41 | date = May 2011 | pmid = 21258411 | doi = 10.1038/onc.2010.608 | pmc=3617575}}</ref> NF-ḵB,<ref name="26-Li">{{cite journal | vauthors = Li DQ, Pakala SB, Nair SS, Eswaran J, Kumar R | title = Metastasis-associated protein 1/nucleosome remodeling and histone deacetylase complex in cancer | journal = Cancer Research | volume = 72 | issue = 2 | pages = 387–94 | date = Jan 2012 | pmid = 22253283 | doi = 10.1158/0008-5472.CAN-11-2345 | pmc=3261506}}</ref> HSF1,<ref name="27-Kha">{{cite journal | vauthors = Khaleque MA, Bharti A, Gong J, Gray PJ, Sachdev V, Ciocca DR, Stati A, Fanelli M, Calderwood SK | title = Heat shock factor 1 represses estrogen-dependent transcription through association with MTA1 | journal = Oncogene | volume = 27 | issue = 13 | pages = 1886–93 | date = Mar 2008 | pmid = 17922035 | doi = 10.1038/sj.onc.1210834 }}</ref> HIF-1a,<ref name="28-Yoo">{{cite journal | vauthors = Yoo YG, Kong G, Lee MO | title = Metastasis-associated protein 1 enhances stability of hypoxia-inducible factor-1alpha protein by recruiting histone deacetylase 1 | journal = The EMBO Journal | volume = 25 | issue = 6 | pages = 1231–41 | date = Mar 2006 | pmid = 16511565 | doi = 10.1038/sj.emboj.7601025 | pmc=1422150}}</ref> and Clock/BMAL1 complex,<ref name="29-Li">{{cite journal | vauthors = Li DQ, Pakala SB, Reddy SD, Peng S, Balasenthil S, Deng CX, Lee CC, Rea MA, Kumar R | title = Metastasis-associated protein 1 is an integral component of the circadian molecular machinery | journal = Nature Communications | volume = 4 | pages = 2545 | date = 2013 | pmid = 24089055 | doi = 10.1038/ncomms3545 }}</ref> and inhibited by p53.<ref name="30-Li">{{cite journal | vauthors = Li DQ, Divijendra Natha Reddy S, Pakala SB, Wu X, Zhang Y, Rayala SK, Kumar R | title = MTA1 coregulator regulates p53 stability and function | journal = The Journal of Biological Chemistry | volume = 284 | issue = 50 | pages = 34545–52 | date = Dec 2009 | pmid = 19837670 | doi = 10.1074/jbc.M109.056499 | pmc=2787316}}</ref> Non-genomic mechanisms of MTA1 expression include
post-transcriptional regulations such as ubiquitination by RING-finger ubiquitin-protein
ligase COP1 <ref name="31-li">{{cite journal | vauthors = Li DQ, Ohshiro K, Reddy SD, Pakala SB, Lee MH, Zhang Y, Rayala SK, Kumar R | title = E3 ubiquitin ligase COP1 regulates the stability and functions of MTA1 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 106 | issue = 41 | pages = 17493–8 | date = Oct 2009 | pmid = 19805145 | doi = 10.1073/pnas.0908027106 | pmc=2762678}}</ref> or interaction with tumor suppressor ARF [24] or micro-RNAs such as
miR-30c, miR-661 and miR-125a-3p.<ref name="32-zhang">{{cite journal | vauthors = Zhang Y, Wang XF | title = Post-transcriptional regulation of MTA family by microRNAs in the context of cancer | journal = Cancer Metastasis Reviews | volume = 33 | issue = 4 | pages = 1011–6 | date = Dec 2014 | pmid = 25332146 | doi = 10.1007/s10555-014-9526-0 | pmc=4245459}}</ref><ref name="33-Kong">{{cite journal | vauthors = Kong X, Xu X, Yan Y, Guo F, Li J, Hu Y, Zhou H, Xun Q | title = Estrogen regulates the tumour suppressor MiRNA-30c and its target gene, MTA-1, in endometrial cancer | journal = PLoS One | volume = 9 | issue = 3 | pages = e90810 | date = 2014 | pmid = 24595016 | doi = 10.1371/journal.pone.0090810 | pmc=3940948}}</ref><ref name="34-reddy">{{cite journal | vauthors = Reddy SD, Pakala SB, Ohshiro K, Rayala SK, Kumar R | title = MicroRNA-661, a c/EBPalpha target, inhibits metastatic tumor antigen 1 and regulates its functions | journal = Cancer Research | volume = 69 | issue = 14 | pages = 5639–42 | date = Jul 2009 | pmid = 19584269 | doi = 10.1158/0008-5472.CAN-09-0898 | pmc=2721803}}</ref><ref name="35-zhang">{{cite journal | vauthors = Zhang H, Zhu X, Li N, Li D, Sha Z, Zheng X, Wang H | title = miR-125a-3p targets MTA1 to suppress NSCLC cell proliferation, migration, and invasion | journal = Acta Biochimica et Biophysica Sinica | volume = 47 | issue = 7 | pages = 496–503 | date = Jul 2015 | pmid = 25998575 | doi = 10.1093/abbs/gmv039 }}</ref>

== Targets ==

Functions of MTA1 are regulated by its post-translational modifications, modulating the roles of effector molecules, interacting with other regulatory proteins and chromatin remodeling machinery, and modulating the expression of target genes via interacting with the components of the NuRD complex including HDACs.<ref name="6-Li" /><ref name="15-mil" /><ref name="16-alq" />

MTA1 suppresses transcription of breast cancer type 1 susceptibility gene,<ref name="36-Molli">{{cite journal | vauthors = Molli PR, Singh RR, Lee SW, Kumar R | title = MTA1-mediated transcriptional repression of BRCA1 tumor suppressor gene | journal = Oncogene | volume = 27 | issue = 14 | pages = 1971–80 | date = Mar 2008 | pmid = 17922032 | doi = 10.1038/sj.onc.1210839 | pmc=2705285}}</ref> PTEN,<ref name="37-Reddy">{{cite journal | vauthors = Reddy SD, Pakala SB, Molli PR, Sahni N, Karanam NK, Mudvari P, Kumar R | title = Metastasis-associated protein 1/histone deacetylase 4-nucleosome remodeling and deacetylase complex regulates phosphatase and tensin homolog gene expression and function | journal = The Journal of Biological Chemistry | volume = 287 | issue = 33 | pages = 27843–50 | date = Aug 2012 | pmid = 22700976 | doi = 10.1074/jbc.M112.348474 | pmc=3431680}}</ref> p21<sup>WAF</sup>,<ref name="38_li">{{cite journal | vauthors = Li DQ, Pakala SB, Reddy SD, Ohshiro K, Peng SH, Lian Y, Fu SW, Kumar R | title = Revelation of p53-independent function of MTA1 in DNA damage response via modulation of the p21 WAF1-proliferating cell nuclear antigen pathway | journal = The Journal of Biological Chemistry | volume = 285 | issue = 13 | pages = 10044–52 | date = Mar 2010 | pmid = 20071335 | doi = 10.1074/jbc.M109.079095 | pmc=2843167}}</ref> guanine nucleotide-binding protein G(i) subunit alpha-2,<ref name="19-Ohshiro"/> SMAD family member 7,<ref name="39-Salot">{{cite journal | vauthors = Salot S, Gude R | title = MTA1-mediated transcriptional repression of SMAD7 in breast cancer cell lines | journal = European Journal of Cancer | volume = 49 | issue = 2 | pages = 492–9 | date = Jan 2013 | pmid = 22841502 | doi = 10.1016/j.ejca.2012.06.019 }}</ref> nuclear receptor subfamily 4 group A member 1,<ref name="40-yU">{{cite journal | vauthors = Yu L, Su YS, Zhao J, Wang H, Li W | title = Repression of NR4A1 by a chromatin modifier promotes docetaxel resistance in PC-3 human prostate cancer cells | journal = FEBS Letters | volume = 587 | issue = 16 | pages = 2542–51 | date = Aug 2013 | pmid = 23831020 | doi = 10.1016/j.febslet.2013.06.029 }}</ref> and homeobox protein SIX3,<ref name="41-Kumar">{{cite journal | vauthors = Kumar R, Balasenthil S, Manavathi B, Rayala SK, Pakala SB | title = Metastasis-associated protein 1 and its short form variant stimulates Wnt1 transcription through promoting its derepression from Six3 corepressor | journal = Cancer Research | volume = 70 | issue = 16 | pages = 6649–58 | date = Aug 2010 | pmid = 20682799 | doi = 10.1158/0008-5472.CAN-10-0909 | pmc=3711655}}</ref> and represses BCL11B<ref name="42-Cis">{{cite journal | vauthors = Cismasiu VB, Adamo K, Gecewicz J, Duque J, Lin Q, Avram D | title = BCL11B functionally associates with the NuRD complex in T lymphocytes to repress targeted promoter | journal = Oncogene | volume = 24 | issue = 45 | pages = 6753–64 | date = Oct 2005 | pmid = 16091750 | doi = 10.1038/sj.onc.1208904 }}</ref>  as well as E-cadherin expression.<ref name="43-Weng">{{cite journal | vauthors = Weng W, Yin J, Zhang Y, Qiu J, Wang X | title = Metastasis-associated protein 1 promotes tumor invasion by downregulation of E-cadherin | journal = International Journal of Oncology | volume = 44 | issue = 3 | pages = 812–8 | date = Mar 2014 | pmid = 24424621 | doi = 10.3892/ijo.2014.2253 }}</ref><ref name="44-Dan">{{cite journal | vauthors = Dannenmann C, Shabani N, Friese K, Jeschke U, Mylonas I, Brüning A | title = The metastasis-associated gene MTA1 is upregulated in advanced ovarian cancer, represses ERbeta, and enhances expression of oncogenic cytokine GRO | journal = Cancer Biology & Therapy | volume = 7 | issue = 9 | pages = 1460–7 | date = Sep 2008 | pmid = 18719363 | doi=10.4161/cbt.7.9.6427}}</ref>

MTA1 is a dual coregulatory as it stimulates the transcription of Stat3,<ref name="45-Pakala">{{cite journal | vauthors = Pakala SB, Rayala SK, Wang RA, Ohshiro K, Mudvari P, Reddy SD, Zheng Y, Pires R, Casimiro S, Pillai MR, Costa L, Kumar R | title = MTA1 promotes STAT3 transcription and pulmonary metastasis in breast cancer | journal = Cancer Research | volume = 73 | issue = 12 | pages = 3761–70 | date = Jun 2013 | pmid = 23580571 | doi = 10.1158/0008-5472.CAN-12-3998 | pmc=3686857}}</ref> breast cancer-amplified sequence 3,<ref name="46-Gururaj">{{cite journal | vauthors = Gururaj AE, Singh RR, Rayala SK, Holm C, den Hollander P, Zhang H, Balasenthil S, Talukder AH, Landberg G, Kumar R | title = MTA1, a transcriptional activator of breast cancer amplified sequence 3 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 17 | pages = 6670–5 | date = Apr 2006 | pmid = 16617102 | doi = 10.1073/pnas.0601989103 | pmc=1458939}}</ref> FosB,<ref name="25-Pakala" /> paired box gene 5,<ref name="47-bala">{{cite journal | vauthors = Balasenthil S, Gururaj AE, Talukder AH, Bagheri-Yarmand R, Arrington T, Haas BJ, Braisted JC, Kim I, Lee NH, Kumar R | title = Identification of Pax5 as a target of MTA1 in B-cell lymphomas | journal = Cancer Research | volume = 67 | issue = 15 | pages = 7132–8 | date = Aug 2007 | pmid = 17671180 | doi = 10.1158/0008-5472.CAN-07-0750 }}</ref> transglutaminase 2,<ref name="48-Ganta">{{cite journal | vauthors = Ghanta KS, Pakala SB, Reddy SD, Li DQ, Nair SS, Kumar R | title = MTA1 coregulation of transglutaminase 2 expression and function during inflammatory response | journal = The Journal of Biological Chemistry | volume = 286 | issue = 9 | pages = 7132–8 | date = Mar 2011 | pmid = 21156794 | doi = 10.1074/jbc.M110.199273 | pmc=3044970}}</ref> myeloid differentiation primary response 88,<ref name="49-Pakala">{{cite journal | vauthors = Pakala SB, Reddy SD, Bui-Nguyen TM, Rangparia SS, Bommana A, Kumar R | title = MTA1 coregulator regulates LPS response via MyD88-dependent signaling | journal = The Journal of Biological Chemistry | volume = 285 | issue = 43 | pages = 32787–92 | date = Oct 2010 | pmid = 20702415 | doi = 10.1074/jbc.M110.151340 | pmc=2963354}}</ref> tumor suppressorp14/p19ARF,<ref name="24-Li" /><ref name="50-Li">{{cite journal | vauthors = Li DQ, Kumar R | title = Mi-2/NuRD complex making inroads into DNA-damage response pathway | journal = Cell Cycle | volume = 9 | issue = 11 | pages = 2071–9 | date = Jun 2010 | pmid = 20505336 | doi=10.4161/cc.9.11.11735 | pmc=3631012}}</ref> tyrosine hydroxylase,<ref name="51-Reddy">{{cite journal | vauthors = Reddy SD, Rayala SK, Ohshiro K, Pakala SB, Kobori N, Dash P, Yun S, Qin J, O'Malley BW, Kumar R | title = Multiple coregulatory control of tyrosine hydroxylase gene transcription | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 108 | issue = 10 | pages = 4200–5 | date = Mar 2011 | pmid = 21368136 | doi = 10.1073/pnas.1101193108 | pmc=3054001}}</ref> clock gene CRY1,<ref name="29-Li" /> SUMO2,<ref name="20-Sumo" /> and Wnt1 and rhodopsin due to release of their transcriptional inhibition by homeodomain protein Six3,<ref name="41-Kumar" /><ref name="52-Mana">{{cite journal | vauthors = Manavathi B, Peng S, Rayala SK, Talukder AH, Wang MH, Wang RA, Balasenthil S, Agarwal N, Frishman LJ, Kumar R | title = Repression of Six3 by a corepressor regulates rhodopsin expression | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = 32 | pages = 13128–33 | date = Aug 2007 | pmid = 17666527 | doi = 10.1073/pnas.0705878104 | pmc=1941821}}</ref>

MTA1 interacts with ERα and coregulatory factors such as MAT1,<ref name="53-Talu">{{cite journal | vauthors = Talukder AH, Mishra SK, Mandal M, Balasenthil S, Mehta S, Sahin AA, Barnes CJ, Kumar R | title = MTA1 interacts with MAT1, a cyclin-dependent kinase-activating kinase complex ring finger factor, and regulates estrogen receptor transactivation functions | journal = The Journal of Biological Chemistry | volume = 278 | issue = 13 | pages = 11676–85 | date = Mar 2003 | pmid = 12527756 | doi = 10.1074/jbc.M209570200 }}</ref> MICoA,<ref name="54-mishra">{{cite journal | vauthors = Mishra SK, Mazumdar A, Vadlamudi RK, Li F, Wang RA, Yu W, Jordan VC, Santen RJ, Kumar R | title = MICoA, a novel metastasis-associated protein 1 (MTA1) interacting protein coactivator, regulates estrogen receptor-alpha transactivation functions | journal = The Journal of Biological Chemistry | volume = 278 | issue = 21 | pages = 19209–19 | date = May 2003 | pmid = 12639951 | doi = 10.1074/jbc.M301968200 }}</ref> NRIF3 [55]<ref name="55-Talu">{{cite journal | vauthors = Talukder AH, Gururaj A, Mishra SK, Vadlamudi RK, Kumar R | title = Metastasis-associated protein 1 interacts with NRIF3, an estrogen-inducible nuclear receptor coregulator | journal = Molecular and Cellular Biology | volume = 24 | issue = 15 | pages = 6581–91 | date = Aug 2004 | pmid = 15254226 | doi = 10.1128/MCB.24.15.6581-6591.2004 | pmc=444867}}</ref> and LMO4， [56],<ref name="56-Singh">{{cite journal | vauthors = Singh RR, Barnes CJ, Talukder AH, Fuqua SA, Kumar R | title = Negative regulation of estrogen receptor alpha transactivation functions by LIM domain only 4 protein | journal = Cancer Research | volume = 65 | issue = 22 | pages = 10594–601 | date = Nov 2005 | pmid = 16288053 | doi = 10.1158/0008-5472.CAN-05-2268 }}</ref> which inhibits ER transactivation activity.<ref name="11-mazumdar" /> MTA1 also deacetylate its target proteins such as p53 and HIF and modulates their transactivation functions.<ref name="57-Moon">{{cite journal | vauthors = Moon HE, Cheon H, Lee MS | title = Metastasis-associated protein 1 inhibits p53-induced apoptosis | journal = Oncology Reports | volume = 18 | issue = 5 | pages = 1311–4 | date = Nov 2007 | pmid = 17914590 | doi = 10.3892/or.18.5.1311 }}</ref><ref name="58-Moon">{{cite journal | vauthors = Moon HE, Cheon H, Chun KH, Lee SK, Kim YS, Jung BK, Park JA, Kim SH, Jeong JW, Lee MS | title = Metastasis-associated protein 1 enhances angiogenesis by stabilization of HIF-1alpha | journal = Oncology Reports | volume = 16 | issue = 4 | pages = 929–35 | date = Oct 2006 | pmid = 16969516 | doi = 10.3892/or.16.4.929 }}</ref> Furthermore, MTA1 could potentially modulate the expression of target genes through the microRNA network as MTA1 knockdown results modulation of miR-210, miR-125b, miR-194, miR-103, and miR-500.<ref name="59-Zhu">{{cite journal | vauthors = Zhu X, Zhang X, Wang H, Song Q, Zhang G, Yang L, Geng J, Li X, Yuan Y, Chen L | title = MTA1 gene silencing inhibits invasion and alters the microRNA expression profile of human lung cancer cells | journal = Oncology Reports | volume = 28 | issue = 1 | pages = 218–24 | date = Jul 2012 | pmid = 22576802 | doi = 10.3892/or.2012.1770 }}</ref><ref name="60-Li">{{cite journal | vauthors = Li Y, Chao Y, Fang Y, Wang J, Wang M, Zhang H, Ying M, Zhu X, Wang H | title = MTA1 promotes the invasion and migration of non-small cell lung cancer cells by downregulating miR-125b | journal = Journal of Experimental & Clinical Cancer Research | volume = 32 | pages = 33 | date = 29 May 2013 | pmid = 23718732 | doi = 10.1186/1756-9966-32-33 | pmc=3671210}}</ref>

==Cellular functions==
MTA1 modulates the expression of target genes due to its ability to act as a corepressor or coactivator. MTA1 targets and/or effector pathways regulate pathways with cellular functions in both normal and cancer cells.<ref name="8-sen" /><ref name="9-sen" /> Physiological functions of MTA1 include: its role in the brain due to MTA1 interactions with DJ1<ref name="50-Li" /> and endophilin-3;<ref name="61-Ara">{{cite journal | vauthors = Aramaki Y, Ogawa K, Toh Y, Ito T, Akimitsu N, Hamamoto H, Sekimizu K, Matsusue K, Kono A, Iguchi H, Takiguchi S | title = Direct interaction between metastasis-associated protein 1 and endophilin 3 | journal = FEBS Letters | volume = 579 | issue = 17 | pages = 3731–6 | date = Jul 2005 | pmid = 15978591 | doi = 10.1016/j.febslet.2005.05.069 }}</ref> regulation of Rhodopsin expression in the murine eye; modifier of circadian rhythm due to MTA1 interactions with the CLOCK-BMAL1 complex and stimulation of Cry-transcription; in heart development due to MTA1-FOG2 interaction; in mammary gland development as MTA1 depletion leads to ductal hypobranching, in spermatogenesis; in immunomodulation due to differential effects on the expression of cytokines in the resting and activated macrophage; in liver regeneration following hepatic injury; differentiation of mesenchymal stem cells into osteogenic axis; and a component of DNA-damage response.<ref name="8-sen" /> In cancer cells, MTA1 and its downstream effectors regulate genes and/or pathways with roles in transformation, invasion, survival, angiogenesis, epithelial-to-mesenchymal transition, metastasis, DNA damage response, and hormone-independence of breast cancer.<ref name="6-Li" /><ref name="9-sen" />

==Notes==
{{Academic-written review
| wikidate = 2016
| journal = [[Gene (journal)|Gene]]
| title   = {{#property:P1476|from=Q28273245}}
| authors = {{#property:P2093|from=Q28273245}}
| date    = {{#property:P577|from=Q28273245}}
| volume  = {{#property:P478|from=Q28273245}}
| issue   = {{#property:P433|from=Q28273245}}
| pages   = {{#property:P304|from=Q28273245}}
| doi     = {{#property:P356|from=Q28273245}}
| pmid    = {{#property:P698|from=Q28273245}}
| pmc    = {{#property:P932|from=Q28273245}}
}}

== References ==
{{reflist|33em}}

== External links ==
* {{MeshName|MTA1+protein,+human}}

{{PDB Gallery|geneid=9112}}
{{Transcription factors|g2}}
{{NLM content}}

[[Category:Transcription factors]]