메뉴 건너뛰기




Volumn 78, Issue 8, 2004, Pages 3805-3810

Transactivator Protein BICP0 of Bovine Herpesvirus 1 (BHV-1) Is Blocked by Prostaglandin D2 (PGD2), Which Points to a Mechanism for PGD2-Mediated Inhibition of BHV-1 Replication

Author keywords

[No Author keywords available]

Indexed keywords

BETA GALACTOSIDASE; COMPLEMENTARY DNA; IMMEDIATE EARLY PROTEIN; LIPOCALIN; PROSTAGLANDIN D SYNTHASE; PROSTAGLANDIN D2; PROTEIN BICPO; TRANSACTIVATOR PROTEIN; UNCLASSIFIED DRUG;

EID: 1842536999     PISSN: 0022538X     EISSN: None     Source Type: Journal    
DOI: 10.1128/JVI.78.8.3805-3810.2004     Document Type: Article
Times cited : (4)

References (57)
  • 1
    • 0019973654 scopus 로고
    • The effect of prostaglandins on the multiplication and cell-to-cell spread of herpes simplex virus type 2 in vitro
    • Baker, D. A., J. Thomas, J. Epstein, D. Possilico, and M. L. Stone. 1982. The effect of prostaglandins on the multiplication and cell-to-cell spread of herpes simplex virus type 2 in vitro. Am. J. Obstet. Gynecol. 144:346-349.
    • (1982) Am. J. Obstet. Gynecol. , vol.144 , pp. 346-349
    • Baker, D.A.1    Thomas, J.2    Epstein, J.3    Possilico, D.4    Stone, M.L.5
  • 2
    • 0027255909 scopus 로고
    • Elimination of false positives that arise in using the two-hybrid system
    • Bartel, P., C. T. Chien, R. Sternglanz, and S. Fields. 1993. Elimination of false positives that arise in using the two-hybrid system. BioTechniques 14:920-924.
    • (1993) BioTechniques , vol.14 , pp. 920-924
    • Bartel, P.1    Chien, C.T.2    Sternglanz, R.3    Fields, S.4
  • 4
    • 0024433471 scopus 로고
    • Heat shock stimulates the release of arachidonic acid and the synthesis of prostaglandins and leukotriene B4 in mammalian cells
    • Calderwood, S. K., B. Bornstein, E. K. Farnum, and M. A. Stevenson. 1989. Heat shock stimulates the release of arachidonic acid and the synthesis of prostaglandins and leukotriene B4 in mammalian cells. J. Cell. Physiol. 141:325-333.
    • (1989) J. Cell. Physiol. , vol.141 , pp. 325-333
    • Calderwood, S.K.1    Bornstein, B.2    Farnum, E.K.3    Stevenson, M.A.4
  • 5
    • 0034943516 scopus 로고    scopus 로고
    • Mixed messages: Modulation of inflammation and immune responses by prostaglandins and thromboxanes
    • Coffman, T. M., B. H. Koller, and S. L. Tilley. 2001. Mixed messages: modulation of inflammation and immune responses by prostaglandins and thromboxanes. J. Clin. Investig. 108:15-23.
    • (2001) J. Clin. Investig. , vol.108 , pp. 15-23
    • Coffman, T.M.1    Koller, B.H.2    Tilley, S.L.3
  • 6
    • 0033885498 scopus 로고    scopus 로고
    • Prostaglandins and fatty acids regulate transcriptional signaling via the peroxisome proliferator activated receptor nuclear receptors
    • Dussault, I., and B. M. Forman. 2000. Prostaglandins and fatty acids regulate transcriptional signaling via the peroxisome proliferator activated receptor nuclear receptors. Prostaglandins Other Lipid Mediat. 62:1-13.
    • (2000) Prostaglandins Other Lipid Mediat. , vol.62 , pp. 1-13
    • Dussault, I.1    Forman, B.M.2
  • 7
    • 0034255499 scopus 로고    scopus 로고
    • Inactivation of wild-type p53 tumor suppressor by electrophilic prostaglandins
    • Edes, K., F. A. Fitzpatrick, and P. J. Moos. 2000. Inactivation of wild-type p53 tumor suppressor by electrophilic prostaglandins. Proc. Natl. Acad. Sci. USA 97:9215-9220.
    • (2000) Proc. Natl. Acad. Sci. USA , vol.97 , pp. 9215-9220
    • Edes, K.1    Fitzpatrick, F.A.2    Moos, P.J.3
  • 8
    • 0023759594 scopus 로고
    • Analysis of the functional domains of herpes simplex virus type 1 immediate-early polypeptide Vmw110
    • Everett, R. D. 1988. Analysis of the functional domains of herpes simplex virus type 1 immediate-early polypeptide Vmw110. J. Mol. Biol. 202:87-96.
    • (1988) J. Mol. Biol. , vol.202 , pp. 87-96
    • Everett, R.D.1
  • 9
    • 0033624137 scopus 로고    scopus 로고
    • ICP0, a regulator of herpes simplex virus during lytic and latent infection
    • Everett, R. D. 2000. ICP0, a regulator of herpes simplex virus during lytic and latent infection. Bioessays 22:761-770.
    • (2000) Bioessays , vol.22 , pp. 761-770
    • Everett, R.D.1
  • 10
    • 0031023690 scopus 로고    scopus 로고
    • A novel ubiquitin-specific protease is dynamically associated with the PML nuclear domain and binds to a herpesvirus regulatory protein
    • Everett, R. D., M. Meredith, A. Orr, A. Cross, M. Kathoria, and J. Parkinson. 1997. A novel ubiquitin-specific protease is dynamically associated with the PML nuclear domain and binds to a herpesvirus regulatory protein. EMBO J. 16:1519-1530.
    • (1997) EMBO J. , vol.16 , pp. 1519-1530
    • Everett, R.D.1    Meredith, M.2    Orr, A.3    Cross, A.4    Kathoria, M.5    Parkinson, J.6
  • 11
    • 0027939149 scopus 로고
    • Identification of the bovine herpesvirus 1 Circ protein, a myristylated and virion-associated polypeptide which is not essential for virus replication in cell culture
    • Fraefel, C., M. Ackermann, and M. Schwyzer. 1994. Identification of the bovine herpesvirus 1 Circ protein, a myristylated and virion-associated polypeptide which is not essential for virus replication in cell culture. J. Virol. 68:8082-8088.
    • (1994) J. Virol. , vol.68 , pp. 8082-8088
    • Fraefel, C.1    Ackermann, M.2    Schwyzer, M.3
  • 12
    • 0028334974 scopus 로고
    • Identification and zinc dependence of the bovine herpesvirus 1 transactivator protein BICP0
    • Fraefel, C., J. Zeng, Y. Choffat, M. Engels, M. Schwyzer, and M. Ackermann. 1994. Identification and zinc dependence of the bovine herpesvirus 1 transactivator protein BICP0. J. Virol. 68:3154-3162.
    • (1994) J. Virol. , vol.68 , pp. 3154-3162
    • Fraefel, C.1    Zeng, J.2    Choffat, Y.3    Engels, M.4    Schwyzer, M.5    Ackermann, M.6
  • 13
    • 0035976575 scopus 로고    scopus 로고
    • Prostaglandins and leukotrienes: Advances in eicosanoid biology
    • Funk, C. D. 2001. Prostaglandins and leukotrienes: advances in eicosanoid biology. Science 294:1871-1875.
    • (2001) Science , vol.294 , pp. 1871-1875
    • Funk, C.D.1
  • 15
    • 0028954118 scopus 로고
    • Studies on the transformation of intact yeast cells by the LiAc/SS-DNA/PEG procedure
    • Gietz, R. D., R. H. Schiestl, A. R. Willems, and R. A. Woods. 1995. Studies on the transformation of intact yeast cells by the LiAc/SS-DNA/PEG procedure. Yeast 11:355-360.
    • (1995) Yeast , vol.11 , pp. 355-360
    • Gietz, R.D.1    Schiestl, R.H.2    Willems, A.R.3    Woods, R.A.4
  • 17
    • 0034728444 scopus 로고    scopus 로고
    • Molecular mechanisms of sleep-wake regulation: A role of prostaglandin D2
    • Hayaishi, O. 2000. Molecular mechanisms of sleep-wake regulation: a role of prostaglandin D2. Philos. Trans. R. Soc. Lond. B Biol. Sci. 355:275-280.
    • (2000) Philos. Trans. R. Soc. Lond. B Biol. Sci. , vol.355 , pp. 275-280
    • Hayaishi, O.1
  • 18
    • 0036007458 scopus 로고    scopus 로고
    • Prostaglandin D2 in sleep-wake regulation: Recent progress and perspectives
    • Hayaishi, O., and Y. Urade. 2002. Prostaglandin D2 in sleep-wake regulation: recent progress and perspectives. Neuroscientist 8:12-15.
    • (2002) Neuroscientist , vol.8 , pp. 12-15
    • Hayaishi, O.1    Urade, Y.2
  • 19
    • 0030422719 scopus 로고    scopus 로고
    • Function and regulation of prostaglandin synthase-2
    • Herschman, H. R., S. T. Reddy, and W. Xie. 1997. Function and regulation of prostaglandin synthase-2. Adv. Exp. Med. Biol. 407:61-66.
    • (1997) Adv. Exp. Med. Biol. , vol.407 , pp. 61-66
    • Herschman, H.R.1    Reddy, S.T.2    Xie, W.3
  • 20
    • 0036268003 scopus 로고    scopus 로고
    • Effect of immunosuppression on gene expression in the HSV-1 latently infected mouse trigeminal ganglion
    • Higaki, S., B. M. Gebhardt, W. J. Lukiw, H. W. Thompson, and J. M. Hill. 2002. Effect of immunosuppression on gene expression in the HSV-1 latently infected mouse trigeminal ganglion. Investig. Ophthalmol. Vis. Sci. 43:1862-1869.
    • (2002) Investig. Ophthalmol. Vis. Sci. , vol.43 , pp. 1862-1869
    • Higaki, S.1    Gebhardt, B.M.2    Lukiw, W.J.3    Thompson, H.W.4    Hill, J.M.5
  • 22
    • 0023481280 scopus 로고
    • A ten-minute DNA preparation from yeast efficiently releases autonomous plasmids for transformation of Escherichia coli
    • Hoffman, C. S., and F. Winston. 1987. A ten-minute DNA preparation from yeast efficiently releases autonomous plasmids for transformation of Escherichia coli. Gene 57:267-272.
    • (1987) Gene , vol.57 , pp. 267-272
    • Hoffman, C.S.1    Winston, F.2
  • 24
    • 0031014985 scopus 로고    scopus 로고
    • Interaction of herpes simplex virus 1 alpha regulatory protein ICP0 with elongation factor 1delta: ICP0 affects translational machinery
    • Kawaguchi, Y., R. Bruni, and B. Roizman. 1997. Interaction of herpes simplex virus 1 alpha regulatory protein ICP0 with elongation factor 1delta: ICP0 affects translational machinery. J. Virol. 71:1019-1024.
    • (1997) J. Virol. , vol.71 , pp. 1019-1024
    • Kawaguchi, Y.1    Bruni, R.2    Roizman, B.3
  • 25
    • 0030820342 scopus 로고    scopus 로고
    • Herpes simplex virus 1 alpha regulatory protein ICP0 interacts with and stabilizes the cell cycle regulator cyclin D3
    • Kawaguchi, Y., C. Van Sant, and B. Roizman. 1997. Herpes simplex virus 1 alpha regulatory protein ICP0 interacts with and stabilizes the cell cycle regulator cyclin D3. J. Virol. 71:7328-7336.
    • (1997) J. Virol. , vol.71 , pp. 7328-7336
    • Kawaguchi, Y.1    Van Sant, C.2    Roizman, B.3
  • 26
    • 0030459782 scopus 로고    scopus 로고
    • Recombinant bovine herpesvirus-1 (BHV-1) lacking transactivator protein BICP0 entails lack of glycoprotein C and severely reduced infectivity
    • Köppel, R., C. Fraefel, B. Vogt, L. J. Bello, W. C. Lawrence, and M. Schwyzer. 1996. Recombinant bovine herpesvirus-1 (BHV-1) lacking transactivator protein BICP0 entails lack of glycoprotein C and severely reduced infectivity. Biol. Chem. 377:787-795.
    • (1996) Biol. Chem. , vol.377 , pp. 787-795
    • Köppel, R.1    Fraefel, C.2    Vogt, B.3    Bello, L.J.4    Lawrence, W.C.5    Schwyzer, M.6
  • 27
    • 0031445611 scopus 로고    scopus 로고
    • Immediate-early protein BICP22 of bovine herpesvirus 1 trans-represses viral promoters of different kinetic classes and is itself regulated by BICP0 at transcriptional and posttranscriptional levels
    • Köppel, R., B. Vogt, and M. Schwyzer. 1997. Immediate-early protein BICP22 of bovine herpesvirus 1 trans-represses viral promoters of different kinetic classes and is itself regulated by BICP0 at transcriptional and posttranscriptional levels. Arch. Virol. 142:2447-2464.
    • (1997) Arch. Virol. , vol.142 , pp. 2447-2464
    • Köppel, R.1    Vogt, B.2    Schwyzer, M.3
  • 29
    • 0028268666 scopus 로고
    • Herpes simplex virus type 1 immediate-early protein Vmw110 binds strongly and specifically to a 135-kDa cellular protein
    • Meredith, M., A. Orr, and R. Everett. 1994. Herpes simplex virus type 1 immediate-early protein Vmw110 binds strongly and specifically to a 135-kDa cellular protein. Virology 200:457-469.
    • (1994) Virology , vol.200 , pp. 457-469
    • Meredith, M.1    Orr, A.2    Everett, R.3
  • 30
    • 0022653027 scopus 로고
    • Bovine herpesvirus 1: Molecular and antigenic characteristics of variant viruses isolated from calves with neurological disease
    • Metzler, A. E., A. A. Schudel, and M. Engels. 1986. Bovine herpesvirus 1: molecular and antigenic characteristics of variant viruses isolated from calves with neurological disease. Arch. Virol. 87:205-217.
    • (1986) Arch. Virol. , vol.87 , pp. 205-217
    • Metzler, A.E.1    Schudel, A.A.2    Engels, M.3
  • 31
    • 0034747670 scopus 로고    scopus 로고
    • Reciprocal interactions between human T-lymphotropic virus type 1 and prostaglandins: Implications for viral transmission
    • Moriuchi, M., H. Inoue, and H. Moriuchi. 2001. Reciprocal interactions between human T-lymphotropic virus type 1 and prostaglandins: implications for viral transmission. J. Virol. 75:192-198.
    • (2001) J. Virol. , vol.75 , pp. 192-198
    • Moriuchi, M.1    Inoue, H.2    Moriuchi, H.3
  • 32
    • 0020333851 scopus 로고
    • Prostaglandin D2 in rat brain, spinal cord and pituitary: Basal level and regional distribution
    • Narumiya, S., T. Ogorochi, K. Nakao, and O. Hayaishi. 1982. Prostaglandin D2 in rat brain, spinal cord and pituitary: basal level and regional distribution. Life Sci. 31:2093-2103.
    • (1982) Life Sci. , vol.31 , pp. 2093-2103
    • Narumiya, S.1    Ogorochi, T.2    Nakao, K.3    Hayaishi, O.4
  • 33
    • 0032823306 scopus 로고    scopus 로고
    • Prostanoid receptors: Structures, properties, and functions
    • Narumiya, S., Y. Sugimoto, and F. Ushikubi. 1999. Prostanoid receptors: structures, properties, and functions. Physiol. Rev. 79:1193-1226.
    • (1999) Physiol. Rev. , vol.79 , pp. 1193-1226
    • Narumiya, S.1    Sugimoto, Y.2    Ushikubi, F.3
  • 35
    • 0021269319 scopus 로고
    • Regional distribution of prostaglandins D2, E2, and F2 alpha and related enzymes in postmortem human brain
    • Ogorochi, T., S. Narumiya, N. Mizuno, K. Yamashita, H. Miyazaki, and O. Hayaishi. 1984. Regional distribution of prostaglandins D2, E2, and F2 alpha and related enzymes in postmortem human brain. J. Neurochem. 43:71-82.
    • (1984) J. Neurochem. , vol.43 , pp. 71-82
    • Ogorochi, T.1    Narumiya, S.2    Mizuno, N.3    Yamashita, K.4    Miyazaki, H.5    Hayaishi, O.6
  • 38
    • 0027408807 scopus 로고
    • Inhibition of vesicular stomatitis virus replication by delta 12-prostaglandin J2 is regulated at two separate levels and is associated with induction of stress protein synthesis
    • Pica, F., A. De Marco, F. De Cesare, and M. G. Santoro. 1993. Inhibition of vesicular stomatitis virus replication by delta 12-prostaglandin J2 is regulated at two separate levels and is associated with induction of stress protein synthesis. Antivir. Res. 20:193-208.
    • (1993) Antivir. Res. , vol.20 , pp. 193-208
    • Pica, F.1    De Marco, A.2    De Cesare, F.3    Santoro, M.G.4
  • 41
    • 0034610759 scopus 로고    scopus 로고
    • Anti-inflammatory cyclopentenone prostaglandins are direct inhibitors of IκB kinase
    • Rossi, A., P. Kapahi, G. Natoli, T. Takahashi, Y. Chen, M. Karin, and M. G. Santoro. 2000. Anti-inflammatory cyclopentenone prostaglandins are direct inhibitors of IκB kinase. Nature 403:103-108.
    • (2000) Nature , vol.403 , pp. 103-108
    • Rossi, A.1    Kapahi, P.2    Natoli, G.3    Takahashi, T.4    Chen, Y.5    Karin, M.6    Santoro, M.G.7
  • 42
    • 0030737735 scopus 로고    scopus 로고
    • Antiviral activity of cyclopentenone prostanoids
    • Santoro, M. G. 1997. Antiviral activity of cyclopentenone prostanoids. Trends Microbiol. 5:276-281.
    • (1997) Trends Microbiol. , vol.5 , pp. 276-281
    • Santoro, M.G.1
  • 43
    • 0024510067 scopus 로고
    • Inhibition of virus protein glycosylation as the mechanism of the antiviral action of prostaglandin A in Sendai virus-infected cells
    • Santoro, M. G., C. Amici, G. Elia, A. Benedetto, and E. Garaci. 1989. Inhibition of virus protein glycosylation as the mechanism of the antiviral action of prostaglandin A in Sendai virus-infected cells. J. Gen. Virol. 70:789-800.
    • (1989) J. Gen. Virol. , vol.70 , pp. 789-800
    • Santoro, M.G.1    Amici, C.2    Elia, G.3    Benedetto, A.4    Garaci, E.5
  • 44
    • 0020526816 scopus 로고
    • The relationship between prostaglandins and virus replication: Endogenous prostaglandin synthesis during infection and the effect of exogenous PGA on virus production in different cell lines and in persistently infected cells
    • Santoro, M. G., A. Benedetto, S. Zaniratti, E. Garaci, and B. M. Jaffe. 1983. The relationship between prostaglandins and virus replication: endogenous prostaglandin synthesis during infection and the effect of exogenous PGA on virus production in different cell lines and in persistently infected cells. Prostaglandins 25:353-364.
    • (1983) Prostaglandins , vol.25 , pp. 353-364
    • Santoro, M.G.1    Benedetto, A.2    Zaniratti, S.3    Garaci, E.4    Jaffe, B.M.5
  • 45
    • 0023102239 scopus 로고
    • PGJ2, a new antiviral prostaglandin: Inhibition of Sendai virus replication and alteration of virus protein synthesis
    • Santoro, M. G., M. Fukushima, A. Benedetto, and C. Amici. 1987. PGJ2, a new antiviral prostaglandin: inhibition of Sendai virus replication and alteration of virus protein synthesis. J. Gen. Virol. 68:1153-1158.
    • (1987) J. Gen. Virol. , vol.68 , pp. 1153-1158
    • Santoro, M.G.1    Fukushima, M.2    Benedetto, A.3    Amici, C.4
  • 46
    • 0021061801 scopus 로고
    • Prostaglandin A inhibits the replication of vesicular stomatitis virus: Effect on virus glycoprotein
    • Santoro, M. G., B. M. Jaffe, and M. Esteban. 1983. Prostaglandin A inhibits the replication of vesicular stomatitis virus: effect on virus glycoprotein. J. Gen. Virol. 64:2797-2801.
    • (1983) J. Gen. Virol. , vol.64 , pp. 2797-2801
    • Santoro, M.G.1    Jaffe, B.M.2    Esteban, M.3
  • 47
    • 0037156222 scopus 로고    scopus 로고
    • Search for physical interaction between BICP0 of bovine herpesvirus-1 and p53 tumor suppressor protein
    • Saydam, O., B. Vogt, M. Ackermann, and M. Schwyzer. 2002. Search for physical interaction between BICP0 of bovine herpesvirus-1 and p53 tumor suppressor protein. Vet. Microbiol. 86:95-102.
    • (2002) Vet. Microbiol. , vol.86 , pp. 95-102
    • Saydam, O.1    Vogt, B.2    Ackermann, M.3    Schwyzer, M.4
  • 48
    • 0028298311 scopus 로고
    • BICP22 of bovine herpesvirus 1 is encoded by a spliced 1.7-kb RNA which exhibits immediate-early and late transcription kinetics
    • Schwyzer, M., U. V. Wirth, B. Vogt, and C. Fraefel. 1994. BICP22 of bovine herpesvirus 1 is encoded by a spliced 1.7-kb RNA which exhibits immediate-early and late transcription kinetics. J. Gen. Virol. 75:1703-1711.
    • (1994) J. Gen. Virol. , vol.75 , pp. 1703-1711
    • Schwyzer, M.1    Wirth, U.V.2    Vogt, B.3    Fraefel, C.4
  • 49
    • 0029823459 scopus 로고    scopus 로고
    • Lipid mediator networks in cell signaling: Update and impact of cytokines
    • Serhan, C. N., J. Z. Haeggstrom, and C. C. Leslie. 1996. Lipid mediator networks in cell signaling: update and impact of cytokines. FASEB J. 10:1147-1158.
    • (1996) FASEB J. , vol.10 , pp. 1147-1158
    • Serhan, C.N.1    Haeggstrom, J.Z.2    Leslie, C.C.3
  • 50
    • 0034684216 scopus 로고    scopus 로고
    • Biochemical, structural, genetic, physiological, and pathophysiological features of lipocalin-type prostaglandin D synthase
    • Urade, Y., and O. Hayaishi. 2000. Biochemical, structural, genetic, physiological, and pathophysiological features of lipocalin-type prostaglandin D synthase. Biochim. Biophys. Acta 1482:259-271.
    • (2000) Biochim. Biophys. Acta , vol.1482 , pp. 259-271
    • Urade, Y.1    Hayaishi, O.2
  • 52
    • 0033627825 scopus 로고    scopus 로고
    • Prostaglandin D synthase: Structure and function
    • Urade, Y., and O. Hayaishi. 2000. Prostaglandin D synthase: structure and function. Vitam. Horm. 58:89-120.
    • (2000) Vitam. Horm. , vol.58 , pp. 89-120
    • Urade, Y.1    Hayaishi, O.2
  • 55
    • 0026559553 scopus 로고
    • Immediate-early RNA 2.9 and early RNA 2.6 of bovine herpesvirus 1 are 3′ coterminal and encode a putative zinc finger transactivator protein
    • Wirth, U. V., C. Fraefel, B. Vogt, C. Vlcek, V. Paces, and M. Schwyzer. 1992. Immediate-early RNA 2.9 and early RNA 2.6 of bovine herpesvirus 1 are 3′ coterminal and encode a putative zinc finger transactivator protein. J. Virol. 66:2763-2772.
    • (1992) J. Virol. , vol.66 , pp. 2763-2772
    • Wirth, U.V.1    Fraefel, C.2    Vogt, B.3    Vlcek, C.4    Paces, V.5    Schwyzer, M.6
  • 56
    • 0029160015 scopus 로고
    • Protein-protein interactions between human nuclear lamins expressed in yeast
    • Ye, Q., and H. J. Worman. 1995. Protein-protein interactions between human nuclear lamins expressed in yeast. Exp. Cell Res. 219:292-298.
    • (1995) Exp. Cell Res. , vol.219 , pp. 292-298
    • Ye, Q.1    Worman, H.J.2
  • 57
    • 0034812721 scopus 로고    scopus 로고
    • The bovine herpesvirus 1 immediate-early protein (bICP0) associates with histone deacetylase 1 to activate transcription
    • Zhang, Y., and C. Jones. 2001. The bovine herpesvirus 1 immediate-early protein (bICP0) associates with histone deacetylase 1 to activate transcription. J. Virol. 75:9571-9578.
    • (2001) J. Virol. , vol.75 , pp. 9571-9578
    • Zhang, Y.1    Jones, C.2


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.