IRF8
IRF8| IRF8 | |||||||||||||||||||||||||
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| 식별자 | |||||||||||||||||||||||||
| 에일리어스 | IRF8, H-ICSBP, ICSBP, ICSBP1, IMD32A, IMD32B, IRF-8, 간섭계수 8 | ||||||||||||||||||||||||
| 외부 ID | OMIM: 601565 MGI: 96395 HomoloGene: 1629 GeneCard: IRF8 | ||||||||||||||||||||||||
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| 맞춤법 | |||||||||||||||||||||||||
| 종. | 인간 | 마우스 | |||||||||||||||||||||||
| 엔트레즈 | |||||||||||||||||||||||||
| 앙상블 | |||||||||||||||||||||||||
| 유니프로트 | |||||||||||||||||||||||||
| RefSeq(mRNA) | |||||||||||||||||||||||||
| RefSeq(단백질) | |||||||||||||||||||||||||
| 장소(UCSC) | Chr 16: 85.9 ~85.92 Mb | Chr 8: 121.46 ~121.48 Mb | |||||||||||||||||||||||
| PubMed 검색 | [3] | [4] | |||||||||||||||||||||||
| 위키데이터 | |||||||||||||||||||||||||
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Interferon Consensus Sequence-binding protein (ICSBP)라고도 알려진 Interferon Regulatory factor 8 (IRF8)은 IRF8 [5][6][7]유전자에 의해 인체에서 암호화되는 단백질이다.IRF8은 공통 골수 전구체(CMP)가 단구 전구체 세포로 분화하는 결정을 포함한 혈통 투입 조절 및 골수 세포 성숙에 중요한 역할을 하는 전사 인자이다.
기능.
인터페론 컨센서스 배열결합단백질(ICSBP)은 인터페론 조절인자(IRF) 계열의 전사인자이다.이 패밀리의 단백질은 N 말단 영역에서 보존된 DNA 결합 도메인과 조절 도메인으로 기능하는 발산 C 말단 영역으로 구성된다.IRF 패밀리 단백질은 IFN 자극반응요소(ISRE)에 결합해 I형 IFN에 의해 자극되는 유전자, 즉 IFN-α 및 IFN-β의 발현을 조절한다.IRF 패밀리 단백질은 바이러스 [5]감염에 의해 유도되는 IFN-α 및 IFN-β-의 발현을 제어한다.
녹아웃 연구
CD11cB220Ly6CCD11blow++− 세포 부족으로 밝혀진 바와 같이 IFN 생산 세포(mIPCs)는 ICSBP 녹아웃(KO) 생쥐의 모든 림프 장기에 존재하지 않았다.이와 함께 ICSBP KO 스플렌에서 분리된 CD11c+ 세포는 바이러스 자극에 반응하여 I형 IFN을 생성할 수 없었다.ICSBP KO 마우스도 비장, 림프절 및 흉선에서 CD8alpha 마커(CD8alpha+ DC)를 발현하는 DC 서브셋의 현저한 감소를 보였다.또한 ICSBP 결핍형 CD8alpha+ DC는 WT DC와 비교했을 때 표현형이 현저하게 손상되었다.이들은 매우 낮은 수준의 비용 자극 분자(세포간 접착 분자 ICAM1, CD40, CD80, CD86)와 T 세포 영역 호밍 케모카인 수용체 CCR7을 [8]발현하였다.
임상적 의의
골수세포에서 IRF8은 백스와 [9]Fas의 발현을 조절하여 아포토시스를 조절한다.만성 골수성 백혈병(CML)에서 IRF8은 CML 아포토시스를 [10]중재하기 위해 산세라미다아제를 조절한다.
IRF8은 골수세포에서 고도로 발현되며, 원래 골수세포 [11]분화를 위한 중요한 혈통 특이 전사 인자로 확인되었지만, 최근의 연구는 IRF8이 비록 낮은 수준이지만 비혈구암세포에서도 구성적으로 발현된다는 것을 보여주었다.또한 IRF8은 비혈구세포에서 IFN-γ에 의해 업 조절될 수도 있다.IRF8은 Fas, Bax, FLIP, Jak1, STAT1의 발현을 매개하여 비혈구암세포에서 [12][13][14]아포토시스를 매개한다.
인간 암 유전체 데이터베이스 분석 결과 IRF8은 3131개 종양의 전체 데이터 집합에서 유의하게 증폭되지 않지만 3131개 종양의 전체 데이터 집합에서 유의하게 삭제되어 IRF8이 잠재적으로 [15]인간의 종양 억제제임을 시사한다.분자 분석에 따르면 IRF8 유전자 프로모터는 인간 대장암 [14][16]세포에서 과메틸화되어 있어 이 세포들이 질병을 진전시키기 위해 IRF8 발현을 침묵시키기 위해 DNA 메틸화를 사용할 수 있다.
상호 작용
IRF8은 IRF1[17][18] 및 COPS2와 [19]상호작용하는 것으로 나타났습니다.
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레퍼런스
- ^ a b c GRCh38: 앙상블 릴리즈 89: ENSG00000140968 - 앙상블, 2017년 5월
- ^ a b c GRCm38: 앙상블 릴리즈 89: ENSMUSG000041515 - 앙상블, 2017년 5월
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b "Entrez Gene: IRF8 interferon regulatory factor 8".
- ^ Weisz A, Marx P, Sharf R, Appella E, Driggers PH, Ozato K, Levi BZ (December 1992). "Human interferon consensus sequence binding protein is a negative regulator of enhancer elements common to interferon-inducible genes". J. Biol. Chem. 267 (35): 25589–96. doi:10.1016/S0021-9258(19)74081-2. PMID 1460054.
- ^ Nehyba J, Hrdlicková R, Burnside J, Bose HR (June 2002). "A novel interferon regulatory factor (IRF), IRF-10, has a unique role in immune defense and is induced by the v-Rel oncoprotein". Mol. Cell. Biol. 22 (11): 3942–57. doi:10.1128/MCB.22.11.3942-3957.2002. PMC 133824. PMID 11997525.
- ^ Tamura T, Ozato K (January 2002). "ICSBP/IRF-8: its regulatory roles in the development of myeloid cells". J. Interferon Cytokine Res. 22 (1): 145–52. doi:10.1089/107999002753452755. PMID 11846985.
- ^ Yang J, Hu X, Zimmerman M, Torres CM, Yang D, Smith SB, Liu K (November 2011). "Cutting edge: IRF8 regulates Bax transcription in vivo in primary myeloid cells". J. Immunol. 187 (9): 4426–30. doi:10.4049/jimmunol.1101034. PMC 3197864. PMID 21949018.
- ^ Hu X, Yang D, Zimmerman M, Liu F, Yang J, Kannan S, Burchert A, Szulc Z, Bielawska A, Ozato K, Bhalla K, Liu K (April 2011). "IRF8 regulates acid ceramidase expression to mediate apoptosis and suppresses myelogeneous leukemia". Cancer Res. 71 (8): 2882–91. doi:10.1158/0008-5472.CAN-10-2493. PMC 3078194. PMID 21487040.
- ^ Holtschke T, Löhler J, Kanno Y, Fehr T, Giese N, Rosenbauer F, Lou J, Knobeloch KP, Gabriele L, Waring JF, Bachmann MF, Zinkernagel RM, Morse HC, Ozato K, Horak I (October 1996). "Immunodeficiency and chronic myelogenous leukemia-like syndrome in mice with a targeted mutation of the ICSBP gene". Cell. 87 (2): 307–17. doi:10.1016/S0092-8674(00)81348-3. PMID 8861914. S2CID 18065448.
- ^ Yang D, Wang S, Brooks C, Dong Z, Schoenlein PV, Kumar V, Ouyang X, Xiong H, Lahat G, Hayes-Jordan A, Lazar A, Pollock R, Lev D, Liu K (February 2009). "IFN regulatory factor 8 sensitizes soft tissue sarcoma cells to death receptor-initiated apoptosis via repression of FLICE-like protein expression". Cancer Res. 69 (3): 1080–8. doi:10.1158/0008-5472.CAN-08-2520. PMC 2633427. PMID 19155307.
- ^ Yang D, Thangaraju M, Browning DD, Dong Z, Korchin B, Lev DC, Ganapathy V, Liu K (October 2007). "IFN regulatory factor 8 mediates apoptosis in nonhemopoietic tumor cells via regulation of Fas expression". J. Immunol. 179 (7): 4775–82. doi:10.4049/jimmunol.179.7.4775. PMID 17878376.
- ^ a b Yang D, Thangaraju M, Greeneltch K, Browning DD, Schoenlein PV, Tamura T, Ozato K, Ganapathy V, Abrams SI, Liu K (April 2007). "Repression of IFN regulatory factor 8 by DNA methylation is a molecular determinant of apoptotic resistance and metastatic phenotype in metastatic tumor cells". Cancer Res. 67 (7): 3301–9. doi:10.1158/0008-5472.CAN-06-4068. PMID 17409439.
- ^ "Tumorscape". The Broad Institute. Archived from the original on 2012-04-14. Retrieved 2012-07-05.
- ^ McGough JM, Yang D, Huang S, Georgi D, Hewitt SM, Röcken C, Tänzer M, Ebert MP, Liu K (December 2008). "DNA methylation represses IFN-gamma-induced and signal transducer and activator of transcription 1-mediated IFN regulatory factor 8 activation in colon carcinoma cells". Mol. Cancer Res. 6 (12): 1841–51. doi:10.1158/1541-7786.MCR-08-0280. PMC 2605678. PMID 19074829.
- ^ Schaper F, Kirchhoff S, Posern G, Köster M, Oumard A, Sharf R, Levi BZ, Hauser H (October 1998). "Functional domains of interferon regulatory factor I (IRF-1)". Biochem. J. 335 (1): 147–57. doi:10.1042/bj3350147. PMC 1219763. PMID 9742224.
- ^ Sharf R, Azriel A, Lejbkowicz F, Winograd SS, Ehrlich R, Levi BZ (June 1995). "Functional domain analysis of interferon consensus sequence binding protein (ICSBP) and its association with interferon regulatory factors". J. Biol. Chem. 270 (22): 13063–9. doi:10.1074/jbc.270.22.13063. PMID 7768900.
- ^ Cohen H, Azriel A, Cohen T, Meraro D, Hashmueli S, Bech-Otschir D, Kraft R, Dubiel W, Levi BZ (December 2000). "Interaction between interferon consensus sequence-binding protein and COP9/signalosome subunit CSN2 (Trip15). A possible link between interferon regulatory factor signaling and the COP9/signalosome". J. Biol. Chem. 275 (50): 39081–9. doi:10.1074/jbc.M004900200. PMID 10991940.
일러스트
추가 정보
- Weisz A, Marx P, Sharf R, Appella E, Driggers PH, Ozato K, Levi BZ (1993). "Human interferon consensus sequence binding protein is a negative regulator of enhancer elements common to interferon-inducible genes". J. Biol. Chem. 267 (35): 25589–96. doi:10.1016/S0021-9258(19)74081-2. PMID 1460054.
- Sharf R, Azriel A, Lejbkowicz F, Winograd SS, Ehrlich R, Levi BZ (1995). "Functional domain analysis of interferon consensus sequence binding protein (ICSBP) and its association with interferon regulatory factors". J. Biol. Chem. 270 (22): 13063–9. doi:10.1074/jbc.270.22.13063. PMID 7768900.
- Holtschke T, Löhler J, Kanno Y, Fehr T, Giese N, Rosenbauer F, Lou J, Knobeloch KP, Gabriele L, Waring JF, Bachmann MF, Zinkernagel RM, Morse HC, Ozato K, Horak I (1996). "Immunodeficiency and chronic myelogenous leukemia-like syndrome in mice with a targeted mutation of the ICSBP gene". Cell. 87 (2): 307–17. doi:10.1016/S0092-8674(00)81348-3. PMID 8861914. S2CID 18065448.
- Schaper F, Kirchhoff S, Posern G, Köster M, Oumard A, Sharf R, Levi BZ, Hauser H (1998). "Functional domains of interferon regulatory factor I (IRF-1)". Biochem. J. 335 (1): 147–57. doi:10.1042/bj3350147. PMC 1219763. PMID 9742224.
- Li W, Nagineni CN, Ge H, Efiok B, Chepelinsky AB, Egwuagu CE (1999). "Interferon consensus sequence-binding protein is constitutively expressed and differentially regulated in the ocular lens". J. Biol. Chem. 274 (14): 9686–91. doi:10.1074/jbc.274.14.9686. PMID 10092656.
- Li W, Nagineni CN, Hooks JJ, Chepelinsky AB, Egwuagu CE (1999). "Interferon-gamma signaling in human retinal pigment epithelial cells mediated by STAT1, ICSBP, and IRF-1 transcription factors". Invest. Ophthalmol. Vis. Sci. 40 (5): 976–82. PMID 10102295.
- Rehli M, Poltorak A, Schwarzfischer L, Krause SW, Andreesen R, Beutler B (2000). "PU.1 and interferon consensus sequence-binding protein regulate the myeloid expression of the human Toll-like receptor 4 gene". J. Biol. Chem. 275 (13): 9773–81. doi:10.1074/jbc.275.13.9773. PMID 10734131.
- Cohen H, Azriel A, Cohen T, Meraro D, Hashmueli S, Bech-Otschir D, Kraft R, Dubiel W, Levi BZ (2001). "Interaction between interferon consensus sequence-binding protein and COP9/signalosome subunit CSN2 (Trip15). A possible link between interferon regulatory factor signaling and the COP9/signalosome". J. Biol. Chem. 275 (50): 39081–9. doi:10.1074/jbc.M004900200. PMID 10991940.
- Nehyba J, Hrdlicková R, Burnside J, Bose HR (2002). "A novel interferon regulatory factor (IRF), IRF-10, has a unique role in immune defense and is induced by the v-Rel oncoprotein". Mol. Cell. Biol. 22 (11): 3942–57. doi:10.1128/MCB.22.11.3942-3957.2002. PMC 133824. PMID 11997525.
- Zhu C, Saberwal G, Lu Y, Platanias LC, Eklund EA (2005). "The interferon consensus sequence-binding protein activates transcription of the gene encoding neurofibromin 1". J. Biol. Chem. 279 (49): 50874–85. doi:10.1074/jbc.M405736200. PMID 15371411.
- Liu J, Guan X, Tamura T, Ozato K, Ma X (2005). "Synergistic activation of interleukin-12 p35 gene transcription by interferon regulatory factor-1 and interferon consensus sequence-binding protein". J. Biol. Chem. 279 (53): 55609–17. doi:10.1074/jbc.M406565200. PMID 15489234.
- Barrios-Rodiles M, Brown KR, Ozdamar B, Bose R, Liu Z, Donovan RS, Shinjo F, Liu Y, Dembowy J, Taylor IW, Luga V, Przulj N, Robinson M, Suzuki H, Hayashizaki Y, Jurisica I, Wrana JL (2005). "High-throughput mapping of a dynamic signaling network in mammalian cells". Science. 307 (5715): 1621–5. Bibcode:2005Sci...307.1621B. doi:10.1126/science.1105776. PMID 15761153. S2CID 39457788.
- Xiong H, Li H, Kong HJ, Chen Y, Zhao J, Xiong S, Huang B, Gu H, Mayer L, Ozato K, Unkeless JC (2005). "Ubiquitin-dependent degradation of interferon regulatory factor-8 mediated by Cbl down-regulates interleukin-12 expression". J. Biol. Chem. 280 (25): 23531–9. doi:10.1074/jbc.M414296200. PMID 15837792.
- Zhao J, Kong HJ, Li H, Huang B, Yang M, Zhu C, Bogunovic M, Zheng F, Mayer L, Ozato K, Unkeless J, Xiong H (2006). "IRF-8/interferon (IFN) consensus sequence-binding protein is involved in Toll-like receptor (TLR) signaling and contributes to the cross-talk between TLR and IFN-gamma signaling pathways". J. Biol. Chem. 281 (15): 10073–80. doi:10.1074/jbc.M507788200. PMID 16484229.
- Huang W, Saberwal G, Horvath E, Zhu C, Lindsey S, Eklund EA (2006). "Leukemia-associated, constitutively active mutants of SHP2 protein tyrosine phosphatase inhibit NF1 transcriptional activation by the interferon consensus sequence binding protein". Mol. Cell. Biol. 26 (17): 6311–32. doi:10.1128/MCB.00036-06. PMC 1592828. PMID 16914719.
- Dimberg A, Kårehed K, Nilsson K, Oberg F (2006). "Inhibition of monocytic differentiation by phosphorylation-deficient Stat1 is associated with impaired expression of Stat2, ICSBP/IRF8 and C/EBPepsilon". Scand. J. Immunol. 64 (3): 271–9. doi:10.1111/j.1365-3083.2006.01827.x. PMID 16918696.
- Leonard D, Svenungsson E, Sandling JK, Berggren O, Jönsen A, Bengtsson C, Wang C, Jensen-Urstad K, Granstam SO, Bengtsson AA, Gustafsson JT, Gunnarsson I, Rantapää-Dahlqvist S, Nordmark G, Eloranta ML, Syvänen AC, Rönnblom L (2013). "Coronary Heart Disease in Systemic Lupus Erythematosus Is Associated with Interferon Regulatory Factor 8 Gene Variants". Circ. Cardiovasc. Genet. 6 (3): 255–63. doi:10.1161/CIRCGENETICS.113.000044. PMID 23661672.
- Peng YB, Yerle M, Liu B (2007). "Mapping of nine porcine interferon regulatory factor genes". Anim. Genet. 37 (6): 600–1. doi:10.1111/j.1365-2052.2006.01525.x. PMID 17121613.
- Huang W, Horvath E, Eklund EA (2007). "PU.1, interferon regulatory factor (IRF) 2, and the interferon consensus sequence-binding protein (ICSBP/IRF8) cooperate to activate NF1 transcription in differentiating myeloid cells". J. Biol. Chem. 282 (9): 6629–43. doi:10.1074/jbc.M607760200. PMID 17200120.
- Mattei F, Schiavoni G, Borghi P, Venditti M, Canini I, Sestili P, Pietraforte I, Morse HC, Ramoni C, Belardelli F, Gabriele L (2006). "ICSBP/IRF-8 differentially regulates antigen uptake during dendritic-cell development and affects antigen presentation to CD4+ T cells". Blood. 108 (2): 609–617. doi:10.1182/blood-2005-11-4490. PMID 16569763.
- Schiavoni G, Mattei F, Sestili P, Borghi P, Venditti M, Morse HC, Belardelli F, Gabriele L (2002). "ICSBP is essential for the development of mouse type I interferon-producing cells and for the generation and activation of CD8alpha(+) dendritic cells". J. Exp. Med. 196 (11): 1415–1425. doi:10.1084/jem.20021263. PMC 2194263. PMID 12461077.
외부 링크
- IRF8+단백질+미국국립의학도서관 의학 과목 제목(MeSH)
