Abstract
The translocation E26 transforming-specific (ETS) leukaemia (TEL), alias the ETS variant (ETV6), gene is expressed in most human tissues and encodes a transcriptional repressor. The TEL gene is involved in more than 40 different chromosomal translocations associated with haematological malignancies. As little is known about the function of intact TEL, we searched for TEL-interacting proteins by yeast two-hybrid screening. Among the interacting partners, we identified the histone acetyltransferase protein Tip60 [60 kDa trans-acting regulatory protein of HIV type 1 (Tat)-interacting protein]. The interaction was reproduced in vitro, and in mammalian cells we mapped the interaction regions in TEL to the ETS domain and those in Tip60 to the MYST ('MOZ, Ybf2/Sas3, SAS2 and Tip60', where MOZ stands for male absent on the first, SAS for something about silencing and Ybf2 for identical with SAS2) region. Detailed analysis of the Tip60 MYST domain by introduction of point mutations revealed that an N-terminal C2HC zinc finger was essential for interaction with TEL. Finally, we showed that Tip60 functions in a reporter system as a co-repressor in TEL-mediated transcription repression.
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- Akhtar A., Becker P. B. The histone H4 acetyltransferase MOF uses a C2HC zinc finger for substrate recognition. EMBO Rep. 2001 Feb;2(2):113–118. doi: 10.1093/embo-reports/kve022. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Andersen M. T., Nordentoft I., Hjalgrim L. L., Christiansen C. L., Jakobsen V. D., Hjalgrim H., Pallisgaard N., Madsen H. O., Christiansen M., Ryder L. P. Characterization of t(12;21) breakpoint junctions in acute lymphoblastic leukemia. Leukemia. 2001 May;15(5):858–859. doi: 10.1038/sj.leu.2402095. [DOI] [PubMed] [Google Scholar]
- Bartel F. O., Higuchi T., Spyropoulos D. D. Mouse models in the study of the Ets family of transcription factors. Oncogene. 2000 Dec 18;19(55):6443–6454. doi: 10.1038/sj.onc.1204038. [DOI] [PubMed] [Google Scholar]
- Brady M. E., Ozanne D. M., Gaughan L., Waite I., Cook S., Neal D. E., Robson C. N. Tip60 is a nuclear hormone receptor coactivator. J Biol Chem. 1999 Jun 18;274(25):17599–17604. doi: 10.1074/jbc.274.25.17599. [DOI] [PubMed] [Google Scholar]
- Cavé H., Cacheux V., Raynaud S., Brunie G., Bakkus M., Cochaux P., Preudhomme C., Laï J. L., Vilmer E., Grandchamp B. ETV6 is the target of chromosome 12p deletions in t(12;21) childhood acute lymphocytic leukemia. Leukemia. 1997 Sep;11(9):1459–1464. doi: 10.1038/sj.leu.2400798. [DOI] [PubMed] [Google Scholar]
- Chakrabarti S. R., Nucifora G. The leukemia-associated gene TEL encodes a transcription repressor which associates with SMRT and mSin3A. Biochem Biophys Res Commun. 1999 Nov 2;264(3):871–877. doi: 10.1006/bbrc.1999.1605. [DOI] [PubMed] [Google Scholar]
- Chakrabarti S. R., Sood R., Ganguly S., Bohlander S., Shen Z., Nucifora G. Modulation of TEL transcription activity by interaction with the ubiquitin-conjugating enzyme UBC9. Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7467–7472. doi: 10.1073/pnas.96.13.7467. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chase A., Reiter A., Burci L., Cazzaniga G., Biondi A., Pickard J., Roberts I. A., Goldman J. M., Cross N. C. Fusion of ETV6 to the caudal-related homeobox gene CDX2 in acute myeloid leukemia with the t(12;13)(p13;q12). Blood. 1999 Feb 1;93(3):1025–1031. [PubMed] [Google Scholar]
- Eguchi M., Eguchi-Ishimae M., Tojo A., Morishita K., Suzuki K., Sato Y., Kudoh S., Tanaka K., Setoyama M., Nagamura F. Fusion of ETV6 to neurotrophin-3 receptor TRKC in acute myeloid leukemia with t(12;15)(p13;q25). Blood. 1999 Feb 15;93(4):1355–1363. [PubMed] [Google Scholar]
- Fenrick R., Amann J. M., Lutterbach B., Wang L., Westendorf J. J., Downing J. R., Hiebert S. W. Both TEL and AML-1 contribute repression domains to the t(12;21) fusion protein. Mol Cell Biol. 1999 Oct;19(10):6566–6574. doi: 10.1128/mcb.19.10.6566. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fenrick R., Wang L., Nip J., Amann J. M., Rooney R. J., Walker-Daniels J., Crawford H. C., Hulboy D. L., Kinch M. S., Matrisian L. M. TEL, a putative tumor suppressor, modulates cell growth and cell morphology of ras-transformed cells while repressing the transcription of stromelysin-1. Mol Cell Biol. 2000 Aug;20(16):5828–5839. doi: 10.1128/mcb.20.16.5828-5839.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fields S., Song O. A novel genetic system to detect protein-protein interactions. Nature. 1989 Jul 20;340(6230):245–246. doi: 10.1038/340245a0. [DOI] [PubMed] [Google Scholar]
- Ford A. M., Bennett C. A., Price C. M., Bruin M. C., Van Wering E. R., Greaves M. Fetal origins of the TEL-AML1 fusion gene in identical twins with leukemia. Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4584–4588. doi: 10.1073/pnas.95.8.4584. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Garvie Colin W., Pufall Miles A., Graves Barbara J., Wolberger Cynthia. Structural analysis of the autoinhibition of Ets-1 and its role in protein partnerships. J Biol Chem. 2002 Sep 6;277(47):45529–45536. doi: 10.1074/jbc.M206327200. [DOI] [PubMed] [Google Scholar]
- Gaughan L., Brady M. E., Cook S., Neal D. E., Robson C. N. Tip60 is a co-activator specific for class I nuclear hormone receptors. J Biol Chem. 2001 Oct 8;276(50):46841–46848. doi: 10.1074/jbc.M103710200. [DOI] [PubMed] [Google Scholar]
- Gaughan Luke, Logan Ian R., Cook Susan, Neal David E., Robson Craig N. Tip60 and histone deacetylase 1 regulate androgen receptor activity through changes to the acetylation status of the receptor. J Biol Chem. 2002 May 6;277(29):25904–25913. doi: 10.1074/jbc.M203423200. [DOI] [PubMed] [Google Scholar]
- Golub T. R., Barker G. F., Bohlander S. K., Hiebert S. W., Ward D. C., Bray-Ward P., Morgan E., Raimondi S. C., Rowley J. D., Gilliland D. G. Fusion of the TEL gene on 12p13 to the AML1 gene on 21q22 in acute lymphoblastic leukemia. Proc Natl Acad Sci U S A. 1995 May 23;92(11):4917–4921. doi: 10.1073/pnas.92.11.4917. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Golub T. R., Barker G. F., Lovett M., Gilliland D. G. Fusion of PDGF receptor beta to a novel ets-like gene, tel, in chronic myelomonocytic leukemia with t(5;12) chromosomal translocation. Cell. 1994 Apr 22;77(2):307–316. doi: 10.1016/0092-8674(94)90322-0. [DOI] [PubMed] [Google Scholar]
- Golub T. R., Goga A., Barker G. F., Afar D. E., McLaughlin J., Bohlander S. K., Rowley J. D., Witte O. N., Gilliland D. G. Oligomerization of the ABL tyrosine kinase by the Ets protein TEL in human leukemia. Mol Cell Biol. 1996 Aug;16(8):4107–4116. doi: 10.1128/mcb.16.8.4107. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Guidez F., Petrie K., Ford A. M., Lu H., Bennett C. A., MacGregor A., Hannemann J., Ito Y., Ghysdael J., Greaves M. Recruitment of the nuclear receptor corepressor N-CoR by the TEL moiety of the childhood leukemia-associated TEL-AML1 oncoprotein. Blood. 2000 Oct 1;96(7):2557–2561. [PubMed] [Google Scholar]
- Hsu T., Schulz R. A. Sequence and functional properties of Ets genes in the model organism Drosophila. Oncogene. 2000 Dec 18;19(55):6409–6416. doi: 10.1038/sj.onc.1204033. [DOI] [PubMed] [Google Scholar]
- Iijima Y., Ito T., Oikawa T., Eguchi M., Eguchi-Ishimae M., Kamada N., Kishi K., Asano S., Sakaki Y., Sato Y. A new ETV6/TEL partner gene, ARG (ABL-related gene or ABL2), identified in an AML-M3 cell line with a t(1;12)(q25;p13) translocation. Blood. 2000 Mar 15;95(6):2126–2131. [PubMed] [Google Scholar]
- Ikura T., Ogryzko V. V., Grigoriev M., Groisman R., Wang J., Horikoshi M., Scully R., Qin J., Nakatani Y. Involvement of the TIP60 histone acetylase complex in DNA repair and apoptosis. Cell. 2000 Aug 18;102(4):463–473. doi: 10.1016/s0092-8674(00)00051-9. [DOI] [PubMed] [Google Scholar]
- Imai Y., Kimura T., Murakami A., Yajima N., Sakamaki K., Yonehara S. The CED-4-homologous protein FLASH is involved in Fas-mediated activation of caspase-8 during apoptosis. Nature. 1999 Apr 29;398(6730):777–785. doi: 10.1038/19709. [DOI] [PubMed] [Google Scholar]
- Jacobson R. H., Ladurner A. G., King D. S., Tjian R. Structure and function of a human TAFII250 double bromodomain module. Science. 2000 May 26;288(5470):1422–1425. doi: 10.1126/science.288.5470.1422. [DOI] [PubMed] [Google Scholar]
- Jonsen M. D., Petersen J. M., Xu Q. P., Graves B. J. Characterization of the cooperative function of inhibitory sequences in Ets-1. Mol Cell Biol. 1996 May;16(5):2065–2073. doi: 10.1128/mcb.16.5.2065. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kamine J., Elangovan B., Subramanian T., Coleman D., Chinnadurai G. Identification of a cellular protein that specifically interacts with the essential cysteine region of the HIV-1 Tat transactivator. Virology. 1996 Feb 15;216(2):357–366. doi: 10.1006/viro.1996.0071. [DOI] [PubMed] [Google Scholar]
- Kimura A., Horikoshi M. Tip60 acetylates six lysines of a specific class in core histones in vitro. Genes Cells. 1998 Dec;3(12):789–800. doi: 10.1046/j.1365-2443.1998.00229.x. [DOI] [PubMed] [Google Scholar]
- Kinoshita Ayae, Whelan Christa M., Berezovska Oksana, Hyman Bradley T. The gamma secretase-generated carboxyl-terminal domain of the amyloid precursor protein induces apoptosis via Tip60 in H4 cells. J Biol Chem. 2002 May 24;277(32):28530–28536. doi: 10.1074/jbc.M203372200. [DOI] [PubMed] [Google Scholar]
- Kiriakidou M., Driscoll D. A., Lopez-Guisa J. M., Strauss J. F., 3rd Cloning and expression of primate Daxx cDNAs and mapping of the human gene to chromosome 6p21.3 in the MHC region. DNA Cell Biol. 1997 Nov;16(11):1289–1298. doi: 10.1089/dna.1997.16.1289. [DOI] [PubMed] [Google Scholar]
- Lacronique V., Boureux A., Valle V. D., Poirel H., Quang C. T., Mauchauffé M., Berthou C., Lessard M., Berger R., Ghysdael J. A TEL-JAK2 fusion protein with constitutive kinase activity in human leukemia. Science. 1997 Nov 14;278(5341):1309–1312. doi: 10.1126/science.278.5341.1309. [DOI] [PubMed] [Google Scholar]
- Legube Gaëlle, Linares Laetitia K., Lemercier Claudie, Scheffner Martin, Khochbin Saadi, Trouche Didier. Tip60 is targeted to proteasome-mediated degradation by Mdm2 and accumulates after UV irradiation. EMBO J. 2002 Apr 2;21(7):1704–1712. doi: 10.1093/emboj/21.7.1704. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Li R., Pei H., Watson D. K., Papas T. S. EAP1/Daxx interacts with ETS1 and represses transcriptional activation of ETS1 target genes. Oncogene. 2000 Feb 10;19(6):745–753. doi: 10.1038/sj.onc.1203385. [DOI] [PubMed] [Google Scholar]
- Liu B., Liao J., Rao X., Kushner S. A., Chung C. D., Chang D. D., Shuai K. Inhibition of Stat1-mediated gene activation by PIAS1. Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10626–10631. doi: 10.1073/pnas.95.18.10626. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lopez R. G., Carron C., Oury C., Gardellin P., Bernard O., Ghysdael J. TEL is a sequence-specific transcriptional repressor. J Biol Chem. 1999 Oct 15;274(42):30132–30138. doi: 10.1074/jbc.274.42.30132. [DOI] [PubMed] [Google Scholar]
- Lu K. P., Hanes S. D., Hunter T. A human peptidyl-prolyl isomerase essential for regulation of mitosis. Nature. 1996 Apr 11;380(6574):544–547. doi: 10.1038/380544a0. [DOI] [PubMed] [Google Scholar]
- Lyngsø C., Bouteiller G., Damgaard C. K., Ryom D., Sanchez-Muñoz S., Nørby P. L., Bonven B. J., Jørgensen P. Interaction between the transcription factor SPBP and the positive cofactor RNF4. An interplay between protein binding zinc fingers. J Biol Chem. 2000 Aug 25;275(34):26144–26149. doi: 10.1074/jbc.M003405200. [DOI] [PubMed] [Google Scholar]
- Maroulakou I. G., Bowe D. B. Expression and function of Ets transcription factors in mammalian development: a regulatory network. Oncogene. 2000 Dec 18;19(55):6432–6442. doi: 10.1038/sj.onc.1204039. [DOI] [PubMed] [Google Scholar]
- Peeters P., Wlodarska I., Baens M., Criel A., Selleslag D., Hagemeijer A., Van den Berghe H., Marynen P. Fusion of ETV6 to MDS1/EVI1 as a result of t(3;12)(q26;p13) in myeloproliferative disorders. Cancer Res. 1997 Feb 15;57(4):564–569. [PubMed] [Google Scholar]
- Poirel H., Oury C., Carron C., Duprez E., Laabi Y., Tsapis A., Romana S. P., Mauchauffe M., Le Coniat M., Berger R. The TEL gene products: nuclear phosphoproteins with DNA binding properties. Oncogene. 1997 Jan 23;14(3):349–357. doi: 10.1038/sj.onc.1200829. [DOI] [PubMed] [Google Scholar]
- Romana S. P., Poirel H., Leconiat M., Flexor M. A., Mauchauffé M., Jonveaux P., Macintyre E. A., Berger R., Bernard O. A. High frequency of t(12;21) in childhood B-lineage acute lymphoblastic leukemia. Blood. 1995 Dec 1;86(11):4263–4269. [PubMed] [Google Scholar]
- Sewack G. F., Ellis T. W., Hansen U. Binding of TATA binding protein to a naturally positioned nucleosome is facilitated by histone acetylation. Mol Cell Biol. 2001 Feb;21(4):1404–1415. doi: 10.1128/MCB.21.4.1404-1415.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sharrocks A. D. The ETS-domain transcription factor family. Nat Rev Mol Cell Biol. 2001 Nov;2(11):827–837. doi: 10.1038/35099076. [DOI] [PubMed] [Google Scholar]
- Shurtleff S. A., Buijs A., Behm F. G., Rubnitz J. E., Raimondi S. C., Hancock M. L., Chan G. C., Pui C. H., Grosveld G., Downing J. R. TEL/AML1 fusion resulting from a cryptic t(12;21) is the most common genetic lesion in pediatric ALL and defines a subgroup of patients with an excellent prognosis. Leukemia. 1995 Dec;9(12):1985–1989. [PubMed] [Google Scholar]
- Smith E. R., Eisen A., Gu W., Sattah M., Pannuti A., Zhou J., Cook R. G., Lucchesi J. C., Allis C. D. ESA1 is a histone acetyltransferase that is essential for growth in yeast. Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3561–3565. doi: 10.1073/pnas.95.7.3561. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sohal J., Reiter A., Goldman J. M., Cross N. C. Cloning of ZNF237, a novel member of the MYM gene family that maps to human chromosome 13q11-->q12. Cytogenet Cell Genet. 2000;89(1-2):24–28. doi: 10.1159/000015584. [DOI] [PubMed] [Google Scholar]
- Sterner D. E., Berger S. L. Acetylation of histones and transcription-related factors. Microbiol Mol Biol Rev. 2000 Jun;64(2):435–459. doi: 10.1128/mmbr.64.2.435-459.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Still I. H., Cowell J. K. The t(8;13) atypical myeloproliferative disorder: further analysis of the ZNF198 gene and lack of evidence for multiple genes disrupted on chromosome 13. Blood. 1998 Aug 15;92(4):1456–1458. [PubMed] [Google Scholar]
- Szymczyna B. R., Arrowsmith C. H. DNA binding specificity studies of four ETS proteins support an indirect read-out mechanism of protein-DNA recognition. J Biol Chem. 2000 Sep 15;275(37):28363–28370. doi: 10.1074/jbc.M004294200. [DOI] [PubMed] [Google Scholar]
- Van Rompaey L., Holland E., Grosveld G. TEL Induces Aggregation in Transformed Cells and Induces Tube Formation in NIH3T3-UCLA Cells. Biochem Biophys Res Commun. 2002 Mar 8;291(4):820–828. doi: 10.1006/bbrc.2002.6513. [DOI] [PubMed] [Google Scholar]
- Wang H., Huang Z. Q., Xia L., Feng Q., Erdjument-Bromage H., Strahl B. D., Briggs S. D., Allis C. D., Wong J., Tempst P. Methylation of histone H4 at arginine 3 facilitating transcriptional activation by nuclear hormone receptor. Science. 2001 May 31;293(5531):853–857. doi: 10.1126/science.1060781. [DOI] [PubMed] [Google Scholar]
- Wang L. C., Kuo F., Fujiwara Y., Gilliland D. G., Golub T. R., Orkin S. H. Yolk sac angiogenic defect and intra-embryonic apoptosis in mice lacking the Ets-related factor TEL. EMBO J. 1997 Jul 16;16(14):4374–4383. doi: 10.1093/emboj/16.14.4374. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wang L. C., Swat W., Fujiwara Y., Davidson L., Visvader J., Kuo F., Alt F. W., Gilliland D. G., Golub T. R., Orkin S. H. The TEL/ETV6 gene is required specifically for hematopoiesis in the bone marrow. Genes Dev. 1998 Aug 1;12(15):2392–2402. doi: 10.1101/gad.12.15.2392. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wasylyk B., Hagman J., Gutierrez-Hartmann A. Ets transcription factors: nuclear effectors of the Ras-MAP-kinase signaling pathway. Trends Biochem Sci. 1998 Jun;23(6):213–216. doi: 10.1016/s0968-0004(98)01211-0. [DOI] [PubMed] [Google Scholar]
- Yaffe M. B., Schutkowski M., Shen M., Zhou X. Z., Stukenberg P. T., Rahfeld J. U., Xu J., Kuang J., Kirschner M. W., Fischer G. Sequence-specific and phosphorylation-dependent proline isomerization: a potential mitotic regulatory mechanism. Science. 1997 Dec 12;278(5345):1957–1960. doi: 10.1126/science.278.5345.1957. [DOI] [PubMed] [Google Scholar]
- Yamamoto T., Horikoshi M. Novel substrate specificity of the histone acetyltransferase activity of HIV-1-Tat interactive protein Tip60. J Biol Chem. 1997 Dec 5;272(49):30595–30598. doi: 10.1074/jbc.272.49.30595. [DOI] [PubMed] [Google Scholar]
- Yan Y., Barlev N. A., Haley R. H., Berger S. L., Marmorstein R. Crystal structure of yeast Esa1 suggests a unified mechanism for catalysis and substrate binding by histone acetyltransferases. Mol Cell. 2000 Nov;6(5):1195–1205. doi: 10.1016/s1097-2765(00)00116-7. [DOI] [PubMed] [Google Scholar]