메뉴 건너뛰기




Volumn 425, Issue 1, 2010, Pages 235-243

Regulatory factors controlling transcription of Saccharomyces cerevisiae IXR1 by oxygen levels: A model of transcriptional adaptation from aerobiosis to hypoxia implicating ROX1 and IXR1 cross-regulation

Author keywords

Hypoxia; IXR1 transcriptional regulation; Oxidative stress; ROX1; Saccharomyces cerevisiae

Indexed keywords

AEROBIOSIS; ANTICANCER DRUG; AUTO-CONTROL; CELL WALLS; CHROMATIN IMMUNOPRECIPITATION; CIS-PLATIN; COREPRESSORS; CYTOCHROME C OXIDASE; DELETION ANALYSIS; ELECTROPHORETIC MOBILITY SHIFT ASSAY; HYPOXIA; HYPOXIC CONDITION; IN-VITRO; LOW LEVEL; MITOCHONDRIAL COMPLEX; MRNA LEVEL; OXYGEN LEVELS; REGULATORY FACTORS; SACCHAROMYCES CEREVISIAE; STRESS RESPONSE; TRANSCRIPTIONAL REGULATION; TRANSCRIPTIONAL REGULATOR;

EID: 72449190235     PISSN: 02646021     EISSN: 14708728     Source Type: Journal    
DOI: 10.1042/BJ20091500     Document Type: Article
Times cited : (17)

References (44)
  • 1
    • 0027248881 scopus 로고
    • Ixr1, a yeast protein that binds to platinated DNA and confers sensitivity to cisplatin
    • Brown, S. J., Kellett, P. J. and Lippard, S. J. (1993) Ixr1, a yeast protein that binds to platinated DNA and confers sensitivity to cisplatin. Science 261, 603-605
    • (1993) Science , vol.261 , pp. 603-605
    • Brown, S.J.1    Kellett, P.J.2    Lippard, S.J.3
  • 2
    • 0030067131 scopus 로고    scopus 로고
    • The HMG-domain protein Ixr1 blocks excision repair of cisplatin-DNA adducts in yeast
    • McA'Nulty, M. M. and Lippard, S. J. (1996) The HMG-domain protein Ixr1 blocks excision repair of cisplatin-DNA adducts in yeast. Mutat. Res. 362, 75-86
    • (1996) Mutat. Res , vol.362 , pp. 75-86
    • McA'Nulty, M.M.1    Lippard, S.J.2
  • 3
    • 0029917564 scopus 로고    scopus 로고
    • Binding of Ixr1, a yeast HMG-domain protein, to cisplatin-DNA adducts in vitro and in vivo
    • McA'Nulty, M. M., Whitehead, J. P. and Lippard, S. J. (1996) Binding of Ixr1, a yeast HMG-domain protein, to cisplatin-DNA adducts in vitro and in vivo. Biochemistry 35, 6089-6099
    • (1996) Biochemistry , vol.35 , pp. 6089-6099
    • McA'Nulty, M.M.1    Whitehead, J.P.2    Lippard, S.J.3
  • 4
    • 0028283154 scopus 로고
    • The ORD1 gene encodes a transcription factor involved in oxygen regulation and is identical to IXR1, a gene that confers cisplatin sensitivity to Saccharomyces cerevisiae
    • Lambert, J. R., Bilanchone, V. W. and Cumsky, M. G. (1994) The ORD1 gene encodes a transcription factor involved in oxygen regulation and is identical to IXR1, a gene that confers cisplatin sensitivity to Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. U.S.A. 91, 7345-7349
    • (1994) Proc. Natl. Acad. Sci. U.S.A , vol.91 , pp. 7345-7349
    • Lambert, J.R.1    Bilanchone, V.W.2    Cumsky, M.G.3
  • 5
    • 0034463392 scopus 로고    scopus 로고
    • Rox1 mediated repression. Oxygen dependent repression in yeast
    • Kastaniotis, A. J. and Zitomer, R. S. (2000) Rox1 mediated repression. Oxygen dependent repression in yeast. Adv. Exp. Med. Biol. 475, 185-195
    • (2000) Adv. Exp. Med. Biol , vol.475 , pp. 185-195
    • Kastaniotis, A.J.1    Zitomer, R.S.2
  • 6
    • 0036271384 scopus 로고    scopus 로고
    • The yeast transcriptome in aerobic and hypoxic conditions: Effects of hap1, rox1, rox3 and srb10 deletions
    • Becerra, M., Lombardía-Ferreira, L. J., Hauser, N. C., Hoheisel, J. D., Tizón, B. and Cerdán, M. E. (2002) The yeast transcriptome in aerobic and hypoxic conditions: effects of hap1, rox1, rox3 and srb10 deletions. Mol. Microbiol. 43, 545-555
    • (2002) Mol. Microbiol , vol.43 , pp. 545-555
    • Becerra, M.1    Lombardía-Ferreira, L.J.2    Hauser, N.C.3    Hoheisel, J.D.4    Tizón, B.5    Cerdán, M.E.6
  • 7
    • 0345305434 scopus 로고    scopus 로고
    • Synergistic repression of anaerobic genes by Mot3 and Rox1 in Saccharomyces cerevisiae
    • Sertil, O., Kapoor, R., Cohen, B. D., Abramova, N. and Lowry, C. V. (2003) Synergistic repression of anaerobic genes by Mot3 and Rox1 in Saccharomyces cerevisiae. Nucleic Acids Res. 31, 5831-5837
    • (2003) Nucleic Acids Res , vol.31 , pp. 5831-5837
    • Sertil, O.1    Kapoor, R.2    Cohen, B.D.3    Abramova, N.4    Lowry, C.V.5
  • 8
    • 18044365236 scopus 로고    scopus 로고
    • Combinatorial repression of the hypoxic genes of Saccharomyces cerevisiae by DNA binding proteins Rox1 and Mot3
    • Klinkenberg, L. G., Mennella, T. A., Luetkenhaus, K. and Zitomer, R. S. (2005) Combinatorial repression of the hypoxic genes of Saccharomyces cerevisiae by DNA binding proteins Rox1 and Mot3. Eukaryotic Cell 4, 649-660
    • (2005) Eukaryotic Cell , vol.4 , pp. 649-660
    • Klinkenberg, L.G.1    Mennella, T.A.2    Luetkenhaus, K.3    Zitomer, R.S.4
  • 9
    • 0033636202 scopus 로고    scopus 로고
    • A Rox1-independent hypoxic pathway in yeast. Antagonistic action of the repressor Ord1 and activator Yap1 for hypoxic expression of the SRP1/ TIR1 gene
    • Bourdineaud, J. P., De Sampaio, G. and Lauquin, G. J. (2000) A Rox1-independent hypoxic pathway in yeast. Antagonistic action of the repressor Ord1 and activator Yap1 for hypoxic expression of the SRP1/ TIR1 gene. Mol. Microbiol. 38, 879-890
    • (2000) Mol. Microbiol , vol.38 , pp. 879-890
    • Bourdineaud, J.P.1    De Sampaio, G.2    Lauquin, G.J.3
  • 10
    • 0028818262 scopus 로고
    • Mutational analysis of Rox1, a DNA-bending repressor of hypoxic genes in Saccharomyces cerevisiae
    • Deckert, J., Rodriguez Torres, A. M., Simon, J. T. and Zitomer, R. S. (1995) Mutational analysis of Rox1, a DNA-bending repressor of hypoxic genes in Saccharomyces cerevisiae. Mol. Cell. Biol. 15, 6109-6117
    • (1995) Mol. Cell. Biol , vol.15 , pp. 6109-6117
    • Deckert, J.1    Rodriguez Torres, A.M.2    Simon, J.T.3    Zitomer, R.S.4
  • 11
    • 0033200165 scopus 로고    scopus 로고
    • Characterization of the DNA binding and bending HMG domain of the yeast hypoxic repressor Rox1
    • Deckert, J., Khalaf, R. A., Hwang, S. M. and Zitomer, R. S. (1999) Characterization of the DNA binding and bending HMG domain of the yeast hypoxic repressor Rox1. Nucleic Acids Res. 27, 3518-3526
    • (1999) Nucleic Acids Res , vol.27 , pp. 3518-3526
    • Deckert, J.1    Khalaf, R.A.2    Hwang, S.M.3    Zitomer, R.S.4
  • 12
    • 33748888161 scopus 로고    scopus 로고
    • A role for sterol levels in oxygen sensing in Saccharomyces cerevisiae
    • Davies, B. S. and Rine, J. (2006) A role for sterol levels in oxygen sensing in Saccharomyces cerevisiae. Genetics 174, 191-201
    • (2006) Genetics , vol.174 , pp. 191-201
    • Davies, B.S.1    Rine, J.2
  • 14
    • 0028302793 scopus 로고
    • HAP1 is nuclear but is bound to a cellular factor in the absence of heme
    • Zhang, L. and Guarente, L. (1994) HAP1 is nuclear but is bound to a cellular factor in the absence of heme. J. Biol. Chem. 269, 14643-14647
    • (1994) J. Biol. Chem , vol.269 , pp. 14643-14647
    • Zhang, L.1    Guarente, L.2
  • 15
    • 0017177548 scopus 로고
    • Yeast cytochrome c messenger RNA: In vitro translation and specific immunoprecipitation of the CYC1 gene product
    • Zitomer, R. S. and Hall, B. D. (1976) Yeast cytochrome c messenger RNA: in vitro translation and specific immunoprecipitation of the CYC1 gene product. J. Biol. Chem. 251, 6320-6326
    • (1976) J. Biol. Chem , vol.251 , pp. 6320-6326
    • Zitomer, R.S.1    Hall, B.D.2
  • 16
    • 0034682078 scopus 로고    scopus 로고
    • Zero background yeast reporter plasmids
    • Melcher, K., Sharma, B., Ding, W. V. and Nolden, M. (2000) Zero background yeast reporter plasmids. Gene 247, 53-61
    • (2000) Gene , vol.247 , pp. 53-61
    • Melcher, K.1    Sharma, B.2    Ding, W.V.3    Nolden, M.4
  • 17
    • 0032528981 scopus 로고    scopus 로고
    • Characterization of promoter regions involved in high expression of KlCYC1
    • Ramil, E., Freire-Picos, M. A. and Cerdán, M. E. (1998) Characterization of promoter regions involved in high expression of KlCYC1. Eur. J. Biochem. 256, 67-74
    • (1998) Eur. J. Biochem , vol.256 , pp. 67-74
    • Ramil, E.1    Freire-Picos, M.A.2    Cerdán, M.E.3
  • 18
    • 0017184389 scopus 로고
    • A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding
    • Bradford, M. M. (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72, 248-254
    • (1976) Anal. Biochem , vol.72 , pp. 248-254
    • Bradford, M.M.1
  • 19
    • 0020529962 scopus 로고
    • Transformation of intact yeast cells treated with alkali cations
    • Ito, H., Fukuda, Y., Murata, K. and Kimura, A. (1983) Transformation of intact yeast cells treated with alkali cations. J. Bacteriol. 153, 163-168
    • (1983) J. Bacteriol , vol.153 , pp. 163-168
    • Ito, H.1    Fukuda, Y.2    Murata, K.3    Kimura, A.4
  • 20
    • 0031947549 scopus 로고    scopus 로고
    • SWI-SNF complex participation in transcriptional activation at a step subsequent to activator binding
    • Ryan, M. P., Jones, R. and Morse, R. H. (1998) SWI-SNF complex participation in transcriptional activation at a step subsequent to activator binding. Mol. Cell. Biol. 18, 1774-1782
    • (1998) Mol. Cell. Biol , vol.18 , pp. 1774-1782
    • Ryan, M.P.1    Jones, R.2    Morse, R.H.3
  • 22
    • 0032762991 scopus 로고    scopus 로고
    • Genome-wide transcriptional analysis of aerobic and anaerobic chemostat cultures of Saccharomyces cerevisiae
    • ter Linde, J. J., Liang, H., Davis, R. W., Steensma, H. Y., van Dijken, J. P. and Pronk, J. T. (1999) Genome-wide transcriptional analysis of aerobic and anaerobic chemostat cultures of Saccharomyces cerevisiae. J. Bacteriol. 181, 7409-7413
    • (1999) J. Bacteriol , vol.181 , pp. 7409-7413
    • ter Linde, J.J.1    Liang, H.2    Davis, R.W.3    Steensma, H.Y.4    van Dijken, J.P.5    Pronk, J.T.6
  • 23
    • 0036135461 scopus 로고    scopus 로고
    • Genomic analyses of anaerobically induced genes in Saccharomyces cerevisiae: Functional roles of Rox1 and other factors in mediating the anoxic response
    • Kwast, K. E., Lai, L. C., Menda, N., James, III, D. T., Aref, S. and Burke, P. V. (2002) Genomic analyses of anaerobically induced genes in Saccharomyces cerevisiae: functional roles of Rox1 and other factors in mediating the anoxic response. J. Bacteriol. 184, 250-265
    • (2002) J. Bacteriol , vol.184 , pp. 250-265
    • Kwast, K.E.1    Lai, L.C.2    Menda, N.3    James III, D.T.4    Aref, S.5    Burke, P.V.6
  • 24
    • 0036317761 scopus 로고    scopus 로고
    • A microarray-assisted screen for potential Hap1 and Rox1 target genes in Saccharomyces cerevisiae
    • Ter Linde, J. J. and Steensma, H. Y. (2002) A microarray-assisted screen for potential Hap1 and Rox1 target genes in Saccharomyces cerevisiae. Yeast 19, 825-840
    • (2002) Yeast , vol.19 , pp. 825-840
    • Ter Linde, J.J.1    Steensma, H.Y.2
  • 25
    • 0026559542 scopus 로고
    • Regulation of gene expression by oxygen in Saccharomyces cerevisiae
    • Zitomer, R. S. and Lowry, C. V. (1992) Regulation of gene expression by oxygen in Saccharomyces cerevisiae. Microbiol. Rev. 56, 1-11
    • (1992) Microbiol. Rev , vol.56 , pp. 1-11
    • Zitomer, R.S.1    Lowry, C.V.2
  • 26
    • 0346433724 scopus 로고    scopus 로고
    • Recruitment of Tup1-Ssn6 by yeast hypoxic genes and chromatin-independent exclusion of TATA binding protein
    • Mennella, T. A., Klinkenberg, L. G. and Zitomer, R. S. (2003) Recruitment of Tup1-Ssn6 by yeast hypoxic genes and chromatin-independent exclusion of TATA binding protein. Eukaryotic Cell 2, 1288-1303
    • (2003) Eukaryotic Cell , vol.2 , pp. 1288-1303
    • Mennella, T.A.1    Klinkenberg, L.G.2    Zitomer, R.S.3
  • 27
    • 0034825082 scopus 로고    scopus 로고
    • 6-transcription factor whose upregulation enhances both sterol uptake and synthesis in aerobically growing Saccharomyces cerevisiae cells
    • 6-transcription factor whose upregulation enhances both sterol uptake and synthesis in aerobically growing Saccharomyces cerevisiae cells. Eur. J. Biochem. 268, 1585-1595
    • (2001) Eur. J. Biochem , vol.268 , pp. 1585-1595
    • Ness, F.1    Bourot, S.2    Regnacq, M.3    Spagnoli, R.4    Berges, T.5    Karst, F.6
  • 28
    • 0034973630 scopus 로고    scopus 로고
    • SUT1p interaction with Cyc8p (Ssn6p) relieves hypoxic genes from Cyc8p-Tup1p repression in Saccharomyces cerevisiae
    • Regnacq, M., Alimardani, P., El Moudni, B. and Berges, T. (2001) SUT1p interaction with Cyc8p (Ssn6p) relieves hypoxic genes from Cyc8p-Tup1p repression in Saccharomyces cerevisiae. Mol. Microbiol. 40, 1085-1096
    • (2001) Mol. Microbiol , vol.40 , pp. 1085-1096
    • Regnacq, M.1    Alimardani, P.2    El Moudni, B.3    Berges, T.4
  • 29
    • 0035253751 scopus 로고    scopus 로고
    • Induction and repression of DAN1 and the family of anaerobic mannoprotein genes in Saccharomyces cerevisiae occurs through a complex array of regulatory sites
    • Cohen, B. D., Sertil, O., Abramova, N. E., Davies, K. J. and Lowry, C. V. (2001) Induction and repression of DAN1 and the family of anaerobic mannoprotein genes in Saccharomyces cerevisiae occurs through a complex array of regulatory sites. Nucleic Acids Res. 29, 799-808
    • (2001) Nucleic Acids Res , vol.29 , pp. 799-808
    • Cohen, B.D.1    Sertil, O.2    Abramova, N.E.3    Davies, K.J.4    Lowry, C.V.5
  • 30
    • 0035107224 scopus 로고    scopus 로고
    • Regulatory mechanisms controlling expression of the DAN/TIR mannoprotein genes during anaerobic remodeling of the cell wall in Saccharomyces cerevisiae
    • Abramova, N. E., Cohen, B. D., Sertil, O., Kapoor, R., Davies, K. J. and Lowry, C. V. (2001) Regulatory mechanisms controlling expression of the DAN/TIR mannoprotein genes during anaerobic remodeling of the cell wall in Saccharomyces cerevisiae. Genetics 157, 1169-1177
    • (2001) Genetics , vol.157 , pp. 1169-1177
    • Abramova, N.E.1    Cohen, B.D.2    Sertil, O.3    Kapoor, R.4    Davies, K.J.5    Lowry, C.V.6
  • 31
    • 0028898763 scopus 로고
    • Multiple elements and auto-repression regulate Rox1, a repressor of hypoxic genes in Saccharomyces cerevisiae
    • Deckert, J., Perini, R., Balasubramanian, B. and Zitomer, R. S. (1995) Multiple elements and auto-repression regulate Rox1, a repressor of hypoxic genes in Saccharomyces cerevisiae. Genetics 139, 1149-1158
    • (1995) Genetics , vol.139 , pp. 1149-1158
    • Deckert, J.1    Perini, R.2    Balasubramanian, B.3    Zitomer, R.S.4
  • 32
    • 17444422796 scopus 로고    scopus 로고
    • The heme activator protein Hap1 represses transcription by a heme-independent mechanism in Saccharomyces cerevisiae
    • Hon, T., Lee, H. C., Hu, Z., Iyer, V. R. and Zhang, L. (2005) The heme activator protein Hap1 represses transcription by a heme-independent mechanism in Saccharomyces cerevisiae. Genetics 169, 1343-1352
    • (2005) Genetics , vol.169 , pp. 1343-1352
    • Hon, T.1    Lee, H.C.2    Hu, Z.3    Iyer, V.R.4    Zhang, L.5
  • 34
    • 0037144396 scopus 로고    scopus 로고
    • Exposure of yeast cells to anoxia induces transient oxidative stress. Implications for the induction of hypoxic genes
    • Dirmeier, R., O'Brien, K. M., Engle, M., Dodd, A., Spears, E. and Poyton, R. O. (2002) Exposure of yeast cells to anoxia induces transient oxidative stress. Implications for the induction of hypoxic genes. J. Biol. Chem. 277, 34773-34784
    • (2002) J. Biol. Chem , vol.277 , pp. 34773-34784
    • Dirmeier, R.1    O'Brien, K.M.2    Engle, M.3    Dodd, A.4    Spears, E.5    Poyton, R.O.6
  • 35
    • 28244500972 scopus 로고    scopus 로고
    • Identification of novel Yap1p and Skn7p binding sites involved in the oxidative stress response of Saccharomyces cerevisiae
    • He, X. J. and Fassler, J. S. (2005) Identification of novel Yap1p and Skn7p binding sites involved in the oxidative stress response of Saccharomyces cerevisiae. Mol. Microbiol. 58, 1454-1467
    • (2005) Mol. Microbiol , vol.58 , pp. 1454-1467
    • He, X.J.1    Fassler, J.S.2
  • 36
    • 0037228781 scopus 로고    scopus 로고
    • A nuclear protein complex containing high mobility group proteins B1 and B2, heat shock cognate protein 70, ERp60, and glyceraldehyde-3-phosphate dehydrogenase is involved in the cytotoxic response to DNA modified by incorporation of anticancer nucleoside analogues
    • Krynetski, E. Y., Krynetskaia, N. F., Bianchi, M. E. and Evans, W. E. (2003) A nuclear protein complex containing high mobility group proteins B1 and B2, heat shock cognate protein 70, ERp60, and glyceraldehyde-3-phosphate dehydrogenase is involved in the cytotoxic response to DNA modified by incorporation of anticancer nucleoside analogues. Cancer Res. 63, 100-106
    • (2003) Cancer Res , vol.63 , pp. 100-106
    • Krynetski, E.Y.1    Krynetskaia, N.F.2    Bianchi, M.E.3    Evans, W.E.4
  • 38
    • 40249107684 scopus 로고    scopus 로고
    • Proteomic screen defines the hepatocyte nuclear factor 1α-binding partners and identifies HMGB1 as a new cofactor of HNF1α
    • Yu, M., Wang, J., Li, W., Yuan, Y. Z., Li, C. Y., Qian, X. H., Xu, W. X., Zhan, Y. Q. and Yang, X. M. (2008) Proteomic screen defines the hepatocyte nuclear factor 1α-binding partners and identifies HMGB1 as a new cofactor of HNF1α. Nucleic Acids Res. 36, 1209-1219
    • (2008) Nucleic Acids Res , vol.36 , pp. 1209-1219
    • Yu, M.1    Wang, J.2    Li, W.3    Yuan, Y.Z.4    Li, C.Y.5    Qian, X.H.6    Xu, W.X.7    Zhan, Y.Q.8    Yang, X.M.9
  • 39
    • 0034810736 scopus 로고    scopus 로고
    • Upc2p and Ecm22p, dual regulators of sterol biosynthesis in Saccharomyces cerevisiae
    • Vik, A. and Rine, J. (2001) Upc2p and Ecm22p, dual regulators of sterol biosynthesis in Saccharomyces cerevisiae. Mol. Cell. Biol. 21, 6395-6405
    • (2001) Mol. Cell. Biol , vol.21 , pp. 6395-6405
    • Vik, A.1    Rine, J.2
  • 41
    • 0035050040 scopus 로고    scopus 로고
    • Reciprocal regulation of anaerobic and aerobic cell wall mannoprotein gene expression in Saccharomyces cerevisiae
    • Abramova, N., Sertil, O., Mehta, S. and Lowry, C. V. (2001) Reciprocal regulation of anaerobic and aerobic cell wall mannoprotein gene expression in Saccharomyces cerevisiae. J. Bacteriol. 183, 2881-2887
    • (2001) J. Bacteriol , vol.183 , pp. 2881-2887
    • Abramova, N.1    Sertil, O.2    Mehta, S.3    Lowry, C.V.4
  • 42
    • 0037031860 scopus 로고    scopus 로고
    • Transcriptional profiling identifies two members of the ATP-binding cassette transporter superfamily required for sterol uptake in yeast
    • Wilcox, L. J., Balderes, D. A., Wharton, B., Tinkelenberg, A. H., Rao, G. and Sturley, S. L. (2002) Transcriptional profiling identifies two members of the ATP-binding cassette transporter superfamily required for sterol uptake in yeast. J. Biol. Chem. 277, 32466-32472
    • (2002) J. Biol. Chem , vol.277 , pp. 32466-32472
    • Wilcox, L.J.1    Balderes, D.A.2    Wharton, B.3    Tinkelenberg, A.H.4    Rao, G.5    Sturley, S.L.6
  • 43
    • 23344435534 scopus 로고    scopus 로고
    • Dual activators of the sterol biosynthetic pathway of Saccharomyces cerevisiae: Similar activation/regulatory domains but different response mechanisms
    • Davies, B. S., Wang, H. S. and Rine, J. (2005) Dual activators of the sterol biosynthetic pathway of Saccharomyces cerevisiae: similar activation/regulatory domains but different response mechanisms. Mol. Cell. Biol. 25, 7375-7385
    • (2005) Mol. Cell. Biol , vol.25 , pp. 7375-7385
    • Davies, B.S.1    Wang, H.S.2    Rine, J.3
  • 44
    • 0037447381 scopus 로고    scopus 로고
    • Transcriptional regulation of YML083c under aerobic and anaerobic conditions
    • Ter Linde, J. J., Regnacq, M. and Steensma, H. Y. (2003) Transcriptional regulation of YML083c under aerobic and anaerobic conditions. Yeast 20, 439-454
    • (2003) Yeast , vol.20 , pp. 439-454
    • Ter Linde, J.J.1    Regnacq, M.2    Steensma, H.Y.3


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.