Abstract
Mipu1 is a novel rat gene recently identified in our lab. Mipu1 cDNA contains a 1,824 bp open reading frame (ORF) and encoded a 608 amino acid protein with an N-terminal Krüppel-associated box (KRAB) domain and classical zinc finger C2H2 motifs in the C-terminus. Mipu1 protein is located in the nuclei. Fused to Gal-4 DNA-binding domain and cotransfected with pG5-luc, Mipu1 played a transcriptional suppressive effect. Deletion analysis with a series of truncated fusion proteins indicated that the KRAB motif was a basal repression domain. Overexpression of Mipu1 in H9c2 myogenic cells inhibited the transcriptional activities of SRE and AP-1. RNAi of Mipu1 in H9c2 myogenic cells activated the transcriptional activities of SRE and AP-1. These results suggested that Mipu1 protein might act as a transcriptional repressor in mitogen-activated protein kinase (MAPK) signaling pathway to mediate cellular functions.
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Plumier JC, Robertson HA, Currie RW (1996) Differential accumulation of mRNA for immediate early genes and heat shock genes in heart after ischaemic injury. J Mol Cell Cardiol 28:1251–1260. doi:10.1006/jmcc.1996.0115
Nelson DP, Wechsler SB, Miura T et al (2002) Myocardial immediate early gene activation after cardiopulmonary bypass with cardiac ischemia-reperfusion. Ann Thorac Surg 73:156–162. doi:10.1016/S0003-4975(01)03303-3
Yuan C, Zhang HL, Liu Y, Wang QP, Xiao XZ (2004) Cloning and characterization of a new gene Mipu1 up-regulated during myocardial ischemia-reperfusion. Prog Biochem Biophys 31:231–236
Jiang L, Tang DL, Wang KK, Zhang HL, Yuan C, Duan DY, Xiao XZ (2007) Functional analysis of a novel KRAB/C2H2 zinc finger protein Mipu1. Biochem Biophys Res Commun 356:829–835. doi:10.1016/j.bbrc.2007.02.138
Berg JM (1990) Zinc finger domains: hypotheses and current knowledge. Annu Rev Biophys Biophys Chem 19:405–421. doi:10.1146/annurev.bb.19.060190.002201
Golden K, Bodmer R (1995) Heart development in Drosophila requires the(segment) polarity gene wingless. Dev Biol 169:619–628. doi:10.1006/dbio.1995.1174
Wu X, Park M, Golden K, Axelrod JD, Bodmer R (1996) The wingless signaling pathway is directly involved in Drosophila heart development. Dev Biol 177:104–116. doi:10.1006/dbio.1996.0149
Kim SS, Chen YM, Leary EO, Witzgall R, Vidal M, Bonventre JV (1996) A novel member of the RING finger family, KRIP-1, associated with the KRAB-A transcriptional repressor domain of zinc finger proteins. Proc Natl Acad Sci USA 93:15299–15304. doi:10.1073/pnas.93.26.15299
Friedman JR, Fredericks WJ, Jensen DE, Speicher DW, Huang XP, Neilson EG, Rauscher FJ (1996) KAP-1, a novel corepressor for highly conserved KRAB repression domain. Genes Dev 10:2067–2078. doi:10.1101/gad.10.16.2067
Treisman R (1996) Regulation of transcription by MAP kinase cascades. Curr Opin Cell Biol 8:205–215. doi:10.1016/S0955-0674(96)80067-6
Drummond IA, Madden SL, Rohwer-Nutter P, Bell GI, Sukhatme VP, Rauscher FJ (1992) Repression of the insulin-like growth factor II gene by the Wilms tumor suppressor WT1. Science 257:674–678. doi:10.1126/science.1323141
Hagen G, Muller S, Beato M, Suske G (1994) Sp1-mediated transcriptional activation is repressed by Sp3. EMBO J 13:3843–3851
Olga O, Reimer S, Tomas P (2002) XSPR-1 and XSPR-2, novel Sp1 related zinc finger containing genes, are dynamically expressed during Xenopus embryogenesis. Mech Dev 115:117–122. doi:10.1016/S0925-4773(02)00086-2
Qi X, Li Y, Xiao J, Yuan W, Yan Y, Wang Y, Liang S, Zhu C, Chen Y, Liu M, Wu X (2006) Activation of transcriptional activities of AP-1 and SRE by a new zinc-finger protein ZNF641. Biochem Biophys Res Commun 339:1155–1164
Schnabl B, Hu K, Mühlbauer M, Hellerbrand C, Stefanovic B, Brenner DA, Schölmerich J (2005) Zinc finger protein 267 is up-regulated during the activation process of human hepatic stellate cells and functions as a negative transcriptional regulator of MMP-10. Biochem Biophys Res Commun 335:87–96. doi:10.1016/j.bbrc.2005.07.043
Li J, Wang Y, Fan X, Mo X, Wang Z, Li Y, Yin Z, Deng Y, Luo N, Zhu C, Liu M, Ma Q, Ocorr K, Yuan W, Wu X (2007) ZNF307, a novel zinc finger gene suppresses p53 and p21 pathway. Biochem Biophys Res Commun 363:895–900. doi:10.1016/j.bbrc.2007.08.180
Li Y, Yang D, Bai Y, Mo X, Huang W, Yuan W, Yin Z, Deng Y, Murashko O, Wang Y, Fan X, Zhu C, Ocorr K, Bodmer R, Wu X (2008) ZNF418, a novel human KRAB/C2H2 zinc finger protein, suppresses MAPK signaling pathway. Mol Cell Biochem 310:141–151. doi:10.1007/s11010-007-9674-4
Gou DM, Wang J, Gao L, Sun Y, Peng X, Huang J, Li WX (2004) Identification and functional analysis of a novel human KRAB/C zinc finger gene ZNF300. Biochim Biophys Acta 1676:203–209
Jeon BN, Yoo JY, Choi WI, Lee CE, Yoon HG, Hur MW (2008) Proto-oncogene FBI-1 (Pokemon/ZBTB7A) represses transcription of the tumor suppressor Rb gene via binding competition with Sp1 and recruitment of corepressors. J Biol Chem [Epub ahead of print]
Peng H, Begg GE, Harper SL, Friedman JR, Speicher DW, Rauscher FJ (2000) Biochemical analysis of the Krüppel-associated box (KRAB) transcriptional repression domain. J Biol Chem 275:18000–18010. doi:10.1074/jbc.M001499200
Agata Y, Matsuda E, Shimizu A (1999) Two novel Kruppel-associated box-containing zinc-finger proteins, KRAZ1 and KRAZ2, repress transcription through functional interaction with the corepressor KAP-1 (TIF1b/KRIP-1). J Biol Chem 274:16412–16422. doi:10.1074/jbc.274.23.16412
Kyriakis JM, Avruch J (2001) Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol Rev 81:807–869
Pearson EJ, Wilsbacher G, Swantek J, Karandikar J, Xu M, Cobb MH (1999) New insights into the control of MAP kinase pathways. Exp Cell Res 253:255–270. doi:10.1006/excr.1999.4687
Treisman R (1996) Regulation of transcription by MAP kinase cascades. Curr Opin Cell Biol 8:205–215. doi:10.1016/S0955-0674(96)80067-6
Wei SG, Yu Y, Zhang ZH, Weiss RM, Felder RB (2008) Mitogen-activated protein kinases mediate upregulation of hypothalamic angiotensin II type 1 receptors in heart failure rats. Hypertension 52:679–686. doi:10.1161/HYPERTENSIONAHA.108.113639
Zhang W, Zhang Y, Edvinsson L, Xu CB (2008) Transcriptional down-regulation of thromboxane A(2) receptor expression via activation of MAPK ERK1/2, p38/NF-kappaB pathways. J Vasc Res 46:162–174. doi:10.1159/000153247
Kaur K, Singh M, Singh N, Jaggi AS (2008) Possible mechanism of rottlerin induced modulation of ischemia reperfusion injury in isolated rat hearts. Biol Pharm Bull 31:1745–1748. doi:10.1248/bpb.31.1745
Muslin AJ (2008) MAPK signalling in cardiovascular health and disease: molecular mechanisms and therapeutic targets. Clin Sci (Lond) 115:203–218. doi:10.1042/CS20070430
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This work was supported by funding from the National Natural Science Foundation of China (30770855, 30672149), the Major National Basic Research Program of China (2007CB512007).
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Guiliang Wang and Xiaoxia Zuo contributed equally to this work.
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Wang, G., Zuo, X., Yuan, C. et al. Mipu1, a novel rat zinc-finger protein, inhibits transcriptional activities of AP-1 and SRE in mitogen-activated protein kinase signaling pathway. Mol Cell Biochem 322, 93–102 (2009). https://doi.org/10.1007/s11010-008-9944-9
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DOI: https://doi.org/10.1007/s11010-008-9944-9