EIF4EBP1 사용 가능한 구조물 PDB 직교 검색: PDBe RCSB PDB ID 코드 목록 1EJ4 , 1WKW , 2JGB , 2JGC , 2V8W , 2V8X , 2V8X, 2V8Y , 3HXG , 3HXI , 3M93 , 3M94 , 3U7X , 4UED , 5BXV
식별자 별칭 EIF4EBP1 외부 ID OMIM : 602223 MGI : 103267 호몰로진 : 3021 GeneCard : EIF4EBP1 직교체 종 인간 마우스 엔트레스 앙상블 유니프로트 RefSeq(mRNA) RefSeq(단백질) 위치(UCSC) Chr 8: 38.03 – 38.06Mb Chr 8: 27.75 – 27.77Mb PubMed 검색[3] [4] 위키다타
진핵 변환 개시 인자 4E 바인딩 단백질 1(일명 4E-BP1)은 인간에서 EIF4EBP1 유전자 에 의해 인코딩 되는 단백질이다.[5]
함수 이 유전자는 번역억제제단백질 계열의 한 구성원을 암호로 한다. 단백질은 진핵 변환 개시 인자 4E(eIF4E )와 직접 상호작용하는데, 이는 mRNA의 5개 끝에 40S 리보솜 서브유닛을 채용하는 멀티유닛 단지의 제한 요소다. 이 단백질과 eIF4E의 상호작용은 복잡한 조립을 억제하고 번역을 억제한다. 이 단백질은 UV 조사와 인슐린 신호를 포함한 다양한 신호에 반응하여 인산염화되며, 그 결과 eIF4E와의 분리 및 캡 의존 mRNA 변환이 활성화된다.[6]
상호작용 EIF4EBP1은 다음과 상호작용 하는 것으로 나타났다.
참조 ^ a b c GRCh38: 앙상블 릴리스 89: ENSG00000187840 - 앙상블 , 2017년 5월^ a b c GRCm38: 앙상블 릴리스 89: ENSMUSG000031490 - 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 .^ Pause A, Belsham GJ, Gingras AC, Donzé O, Lin TA, Lawrence JC, Sonenberg N (November 1994). "Insulin-dependent stimulation of protein synthesis by phosphorylation of a regulator of 5'-cap function". Nature . 371 (6500): 762–767. doi :10.1038/371762a0 . PMID 7935836 . S2CID 4360955 . ^ "Entrez Gene: EIF4EBP1 eukaryotic translation initiation factor 4E binding protein 1" .^ Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature . 437 (7062): 1173–8. doi :10.1038/nature04209 . PMID 16189514 . S2CID 4427026 . ^ Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry" . Mol. Syst. Biol . 3 : 89. doi :10.1038/msb4100134 . PMC 1847948 PMID 17353931 . ^ Mader S, Lee H, Pause A, Sonenberg N (September 1995). "The translation initiation factor eIF-4E binds to a common motif shared by the translation factor eIF-4 gamma and the translational repressors 4E-binding proteins" . Mol. Cell. Biol . 15 (9): 4990–7. doi :10.1128/MCB.15.9.4990 . PMC 230746 PMID 7651417 . ^ Rao RD, Mladek AC, Lamont JD, Goble JM, Erlichman C, James CD, Sarkaria JN (October 2005). "Disruption of parallel and converging signaling pathways contributes to the synergistic antitumor effects of simultaneous mTOR and EGFR inhibition in GBM cells" . Neoplasia . 7 (10): 921–9. doi :10.1593/neo.05361 . PMC 1502028 PMID 16242075 . ^ a b Eguchi S, Tokunaga C, Hidayat S, Oshiro N, Yoshino K, Kikkawa U, Yonezawa K (July 2006). "Different roles for the TOS and RAIP motifs of the translational regulator protein 4E-BP1 in the association with raptor and phosphorylation by mTOR in the regulation of cell size" . Genes Cells . 11 (7): 757–66. doi :10.1111/j.1365-2443.2006.00977.x PMID 16824195 . S2CID 30113895 . ^ Yang D, Brunn GJ, Lawrence JC (June 1999). "Mutational analysis of sites in the translational regulator, PHAS-I, that are selectively phosphorylated by mTOR" . FEBS Lett . 453 (3): 387–90. doi :10.1016/s0014-5793(99)00762-0 PMID 10405182 . S2CID 5023204 . ^ Patel J, McLeod LE, Vries RG, Flynn A, Wang X, Proud CG (June 2002). "Cellular stresses profoundly inhibit protein synthesis and modulate the states of phosphorylation of multiple translation factors". Eur. J. Biochem . 269 (12): 3076–85. doi :10.1046/j.1432-1033.2002.02992.x . PMID 12071973 . ^ Kumar V, Sabatini D, Pandey P, Gingras AC, Majumder PK, Kumar M, Yuan ZM, Carmichael G, Weichselbaum R, Sonenberg N, Kufe D, Kharbanda S (April 2000). "Regulation of the rapamycin and FKBP-target 1/mammalian target of rapamycin and cap-dependent initiation of translation by the c-Abl protein-tyrosine kinase" . J. Biol. Chem . 275 (15): 10779–87. doi :10.1074/jbc.275.15.10779 PMID 10753870 . ^ Kumar V, Pandey P, Sabatini D, Kumar M, Majumder PK, Bharti A, Carmichael G, Kufe D, Kharbanda S (March 2000). "Functional interaction between RAFT1/FRAP/mTOR and protein kinase cdelta in the regulation of cap-dependent initiation of translation" . EMBO J . 19 (5): 1087–97. doi :10.1093/emboj/19.5.1087 . PMC 305647 PMID 10698949 . ^ Gingras AC, Gygi SP, Raught B, Polakiewicz RD, Abraham RT, Hoekstra MF, Aebersold R, Sonenberg N (June 1999). "Regulation of 4E-BP1 phosphorylation: a novel two-step mechanism" . Genes Dev . 13 (11): 1422–37. doi :10.1101/gad.13.11.1422 . PMC 316780 PMID 10364159 . ^ Connolly E, Braunstein S, Formenti S, Schneider RJ (May 2006). "Hypoxia inhibits protein synthesis through a 4E-BP1 and elongation factor 2 kinase pathway controlled by mTOR and uncoupled in breast cancer cells" . Mol. Cell. Biol . 26 (10): 3955–65. doi :10.1128/MCB.26.10.3955-3965.2006 . PMC 1489005 PMID 16648488 . ^ Shen X, Tomoo K, Uchiyama S, Kobayashi Y, Ishida T (October 2001). "Structural and thermodynamic behavior of eukaryotic initiation factor 4E in supramolecular formation with 4E-binding protein 1 and mRNA cap analogue, studied by spectroscopic methods" . Chem. Pharm. Bull . 49 (10): 1299–303. doi :10.1248/cpb.49.1299 PMID 11605658 . ^ Adegoke OA, Chevalier S, Morais JA, Gougeon R, Kimball SR, Jefferson LS, Wing SS, Marliss EB (January 2009). "Fed-state clamp stimulates cellular mechanisms of muscle protein anabolism and modulates glucose disposal in normal men" . Am. J. Physiol. Endocrinol. Metab . 296 (1): E105–13. doi :10.1152/ajpendo.90752.2008 . PMC 2636991 PMID 18957614 . ^ a b Schalm SS, Fingar DC, Sabatini DM, Blenis J (May 2003). "TOS motif-mediated raptor binding regulates 4E-BP1 multisite phosphorylation and function" . Curr. Biol . 13 (10): 797–806. doi :10.1016/s0960-9822(03)00329-4 PMID 12747827 . S2CID 10326807 . ^ a b Hara K, Maruki Y, Long X, Yoshino K, Oshiro N, Hidayat S, Tokunaga C, Avruch J, Yonezawa K (July 2002). "Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action" . Cell . 110 (2): 177–89. doi :10.1016/s0092-8674(02)00833-4 PMID 12150926 . S2CID 6438316 . ^ a b Wang L, Rhodes CJ, Lawrence JC (August 2006). "Activation of mammalian target of rapamycin (mTOR) by insulin is associated with stimulation of 4EBP1 binding to dimeric mTOR complex 1" . J. Biol. Chem . 281 (34): 24293–303. doi :10.1074/jbc.M603566200 PMID 16798736 . ^ a b Wang X, Beugnet A, Murakami M, Yamanaka S, Proud CG (April 2005). "Distinct signaling events downstream of mTOR cooperate to mediate the effects of amino acids and insulin on initiation factor 4E-binding proteins" . Mol. Cell. Biol . 25 (7): 2558–72. doi :10.1128/MCB.25.7.2558-2572.2005 . PMC 1061630 PMID 15767663 . ^ Ha SH, Kim DH, Kim IS, Kim JH, Lee MN, Lee HJ, Kim JH, Jang SK, Suh PG, Ryu SH (December 2006). "PLD2 forms a functional complex with mTOR/raptor to transduce mitogenic signals". Cell. Signal . 18 (12): 2283–91. doi :10.1016/j.cellsig.2006.05.021 . PMID 16837165 . ^ Beugnet A, Wang X, Proud CG (October 2003). "Target of rapamycin (TOR)-signaling and RAIP motifs play distinct roles in the mammalian TOR-dependent phosphorylation of initiation factor 4E-binding protein 1" . J. Biol. Chem . 278 (42): 40717–22. doi :10.1074/jbc.M308573200 PMID 12912989 . ^ Nojima H, Tokunaga C, Eguchi S, Oshiro N, Hidayat S, Yoshino K, Hara K, Tanaka N, Avruch J, Yonezawa K (May 2003). "The mammalian target of rapamycin (mTOR) partner, raptor, binds the mTOR substrates p70 S6 kinase and 4E-BP1 through their TOR signaling (TOS) motif" . J. Biol. Chem . 278 (18): 15461–4. doi :10.1074/jbc.C200665200 PMID 12604610 . ^ Kim DH, Sarbassov DD, Ali SM, King JE, Latek RR, Erdjument-Bromage H, Tempst P, Sabatini DM (July 2002). "mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery" . Cell . 110 (2): 163–75. doi :10.1016/s0092-8674(02)00808-5 PMID 12150925 . S2CID 4656930 . ^ Long X, Lin Y, Ortiz-Vega S, Yonezawa K, Avruch J (April 2005). "Rheb binds and regulates the mTOR kinase" . Curr. Biol . 15 (8): 702–13. doi :10.1016/j.cub.2005.02.053 PMID 15854902 . S2CID 3078706 . ^ Takahashi T, Hara K, Inoue H, Kawa Y, Tokunaga C, Hidayat S, Yoshino K, Kuroda Y, Yonezawa K (September 2000). "Carboxyl-terminal region conserved among phosphoinositide-kinase-related kinases is indispensable for mTOR function in vivo and in vitro" . Genes Cells . 5 (9): 765–75. doi :10.1046/j.1365-2443.2000.00365.x PMID 10971657 . S2CID 39048740 . ^ Burnett PE, Barrow RK, Cohen NA, Snyder SH, Sabatini DM (February 1998). "RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1" . Proc. Natl. Acad. Sci. U.S.A . 95 (4): 1432–7. doi :10.1073/pnas.95.4.1432 PMC 19032 PMID 9465032 . 추가 읽기 Armengol G, Rojo F, Castellví J, Iglesias C, Cuatrecasas M, Pons B, Baselga J, Ramón y Cajal S (2007). "4E-binding protein 1: a key molecular "funnel factor" in human cancer with clinical implications" . Cancer Res . 67 (16): 7551–7555. doi :10.1158/0008-5472.CAN-07-0881 PMID 17699757 . Mader S, Lee H, Pause A, Sonenberg N (1995). "The translation initiation factor eIF-4E binds to a common motif shared by the translation factor eIF-4 gamma and the translational repressors 4E-binding proteins" . Mol. Cell. Biol . 15 (9): 4990–7. doi :10.1128/MCB.15.9.4990 . PMC 230746 PMID 7651417 . Haystead TA, Haystead CM, Hu C, Lin TA, Lawrence JC (1994). "Phosphorylation of PHAS-I by mitogen-activated protein (MAP) kinase. Identification of a site phosphorylated by MAP kinase in vitro and in response to insulin in rat adipocytes" . J. Biol. Chem . 269 (37): 23185–91. doi :10.1016/S0021-9258(17)31637-X PMID 8083223 . Haghighat A, Mader S, Pause A, Sonenberg N (1996). "Repression of cap-dependent translation by 4E-binding protein 1: competition with p220 for binding to eukaryotic initiation factor-4E" . EMBO J . 14 (22): 5701–9. doi :10.1002/j.1460-2075.1995.tb00257.x . PMC 394685 PMID 8521827 . Feigenblum D, Schneider RJ (1996). "Cap-binding protein (eukaryotic initiation factor 4E) and 4E-inactivating protein BP-1 independently regulate cap-dependent translation" . Mol. Cell. Biol . 16 (10): 5450–7. doi :10.1128/MCB.16.10.5450 . PMC 231545 PMID 8816458 . Rousseau D, Gingras AC, Pause A, Sonenberg N (1997). "The eIF4E-binding proteins 1 and 2 are negative regulators of cell growth". Oncogene . 13 (11): 2415–20. PMID 8957083 . Tsukiyama-Kohara K, Vidal SM, Gingras AC, Glover TW, Hanash SM, Heng H, Sonenberg N (1997). "Tissue distribution, genomic structure, and chromosome mapping of mouse and human eukaryotic initiation factor 4E-binding proteins 1 and 2". Genomics . 38 (3): 353–363. doi :10.1006/geno.1996.0638 . PMID 8975712 . Fadden P, Haystead TA, Lawrence JC (1997). "Identification of phosphorylation sites in the translational regulator, PHAS-I, that are controlled by insulin and rapamycin in rat adipocytes" . J. Biol. Chem . 272 (15): 10240–10247. doi :10.1074/jbc.272.15.10240 PMID 9092573 . Brunn GJ, Fadden P, Haystead TA, Lawrence JC (1998). "The mammalian target of rapamycin phosphorylates sites having a (Ser/Thr)-Pro motif and is activated by antibodies to a region near its COOH terminus" . J. Biol. Chem . 272 (51): 32547–32550. doi :10.1074/jbc.272.51.32547 PMID 9405468 . Burnett PE, Barrow RK, Cohen NA, Snyder SH, Sabatini DM (1998). "RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1" . Proc. Natl. Acad. Sci. U.S.A . 95 (4): 1432–1437. doi :10.1073/pnas.95.4.1432 PMC 19032 PMID 9465032 . New L, Jiang Y, Zhao M, Liu K, Zhu W, Flood LJ, Kato Y, Parry GC, Han J (1998). "PRAK, a novel protein kinase regulated by the p38 MAP kinase" . EMBO J . 17 (12): 3372–3384. doi :10.1093/emboj/17.12.3372 . PMC 1170675 PMID 9628874 . Heesom KJ, Avison MB, Diggle TA, Denton RM (1999). "Insulin-stimulated kinase from rat fat cells that phosphorylates initiation factor 4E-binding protein 1 on the rapamycin-insensitive site (serine-111)" . Biochem. J . 336 (1): 39–48. doi :10.1042/bj3360039 . PMC 1219839 PMID 9806882 . Waskiewicz AJ, Johnson JC, Penn B, Mahalingam M, Kimball SR, Cooper JA (1999). "Phosphorylation of the cap-binding protein eukaryotic translation initiation factor 4E by protein kinase Mnk1 in vivo" . Mol. Cell. Biol . 19 (3): 1871–80. doi :10.1128/MCB.19.3.1871 . PMC 83980 PMID 10022874 . Seeley TW, Wang L, Zhen JY (1999). "Phosphorylation of human MAD1 by the BUB1 kinase in vitro". Biochem. Biophys. Res. Commun . 257 (2): 589–595. doi :10.1006/bbrc.1999.0514 . PMID 10198256 . Gingras AC, Gygi SP, Raught B, Polakiewicz RD, Abraham RT, Hoekstra MF, Aebersold R, Sonenberg N (1999). "Regulation of 4E-BP1 phosphorylation: a novel two-step mechanism" . Genes Dev . 13 (11): 1422–1437. doi :10.1101/gad.13.11.1422 . PMC 316780 PMID 10364159 . Yang D, Brunn GJ, Lawrence JC (1999). "Mutational analysis of sites in the translational regulator, PHAS-I, that are selectively phosphorylated by mTOR" . FEBS Lett . 453 (3): 387–390. doi :10.1016/S0014-5793(99)00762-0 PMID 10405182 . S2CID 5023204 . Kim ST, Lim DS, Canman CE, Kastan MB (2000). "Substrate specificities and identification of putative substrates of ATM kinase family members" . J. Biol. Chem . 274 (53): 37538–37543. doi :10.1074/jbc.274.53.37538 PMID 10608806 . Mothe-Satney I, Yang D, Fadden P, Haystead TA, Lawrence JC (2000). "Multiple mechanisms control phosphorylation of PHAS-I in five (S/T)P sites that govern translational repression" . Mol. Cell. Biol . 20 (10): 3558–3567. doi :10.1128/MCB.20.10.3558-3567.2000 . PMC 85648 PMID 10779345 . Mothe-Satney I, Brunn GJ, McMahon LP, Capaldo CT, Abraham RT, Lawrence JC (2000). "Mammalian target of rapamycin-dependent phosphorylation of PHAS-I in four (S/T)P sites detected by phospho-specific antibodies" . J. Biol. Chem . 275 (43): 33836–33843. doi :10.1074/jbc.M006005200 PMID 10942774 . 
