EGR2
Protein 2 ranog odgovora na rast je protein koji je kod ljudi kodiran genom EGR2. EGR2 (znan i kao Krox20) je transkripcijski faktor regulacije, sa tri mjesta vezanja DNK cinkovog prsta, izrazito eksprimiran u populaciji migrirajućih ćelija nervnog grebena.[5][6][7] Kasnije se eksprimira u neuronskim ćelijama kranijalne ganglije izvedene iz grebena. Protein kodiran pomoću Krox20 sadrži dva cinkova prsta tipa cys2his2. Ekspresija Krox20 gena ograničena je na rani razvoj stražnjeg mozga.[6][8] Evolucijski je konzerviran kod kičmenjaka, uključujuči ljude, miševe, kokoši i zebrice.[9] Osim toga, aminokiselinska sekvenca i većina aspekata uzorka embrionskog gena konzervirani su kod kičmenjaka, što dodatno implicira njegovu ulogu u razvoju stražnjeg mozga.[7][10][11][12] Kada se
Krox20 deletira na miševima, sposobnost kodiranja proteina gena Krox20 (uključujući domen vezanja DNK cinkovog prsta) se smanjuje. Ovi miševi ne mogu preživjeti nakon rođenja i pokazuju velike nedostatke stražnjeg mozga.[6][8] Ovi nedostaci uključuju, ali nisu ograničeni na nedostatke u formiranju kranijalnih čulnihih ganglija, djelimičnu fuziju trigeminusog živca (V) s facijalnim (VII) i slušnim (VII) živcima, proksimalni korijeni živaca koji izlaze iz ovih ganglija bili su neorganizirani i isprepleteni jedni s drugima pri ulasku u moždano stablo, a došlo je i do spajanja glosofaringeusog (IX) nervnog kompleksa.[13][14][15]
Aminokiselinska sekvenca
urediDužina polipeptidnog lanca je 476 aminokiselina, а molekulska težina 50.302.[16]
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MMTAKAVDKI | PVTLSGFVHQ | LSDNIYPVED | LAATSVTIFP | NAELGGPFDQ | ||||
| MNGVAGDGMI | NIDMTGEKRS | LDLPYPSSFA | PVSAPRNQTF | TYMGKFSIDP | ||||
| QYPGASCYPE | GIINIVSAGI | LQGVTSPAST | TASSSVTSAS | PNPLATGPLG | ||||
| VCTMSQTQPD | LDHLYSPPPP | PPPYSGCAGD | LYQDPSAFLS | AATTSTSSSL | ||||
| AYPPPPSYPS | PKPATDPGLF | PMIPDYPGFF | PSQCQRDLHG | TAGPDRKPFP | ||||
| CPLDTLRVPP | PLTPLSTIRN | FTLGGPSAGV | TGPGASGGSE | GPRLPGSSSA | ||||
| AAAAAAAAAY | NPHHLPLRPI | LRPRKYPNRP | SKTPVHERPY | PCPAEGCDRR | ||||
| FSRSDELTRH | IRIHTGHKPF | QCRICMRNFS | RSDHLTTHIR | THTGEKPFAC | ||||
| DYCGRKFARS | DERKRHTKIH | LRQKERKSSA | PSASVPAPST | ASCSGGVQPG | ||||
| GTLCSSNSSS | LGGGPLAPCS | SRTRTP |
- Simboli
Funkcija
urediProtein 2 za odgovor na rani rast je transkripcijski faktor s tri tandemska cinkova prsta tipa C2H2. Mutacije u ovom genu povezane su s autosomno dominantnom Charcot-Marie-Toothovom bolesti, tip 1D,[17] Dejerine–Sottasovom bolesti,[18] i kongenitalnom hipomijelinacijskom neuropatijom.[19] Dvije studije povezale su ekspresiju "EGR2" sa proliferacijom osteoprogenitora[20] i ćelijske linije izvedene iz Ewingovog sarkoma, koji je visoko agresivan rak povezan s kostima.[21]
Novo istraživanje sugerira da je Krox20 - ili njegov nedostatak – uzrok muške prijezrelosne ćelavosti.[22]
Reference
uredi- ^ a b c GRCh38: Ensembl release 89: ENSG00000122877 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000037868 - Ensembl, maj 2017
- ^ "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.
- ^ Chavrier P, Janssen-Timmen U, Mattéi MG, Zerial M, Bravo R, Charnay P (februar 1989). "Structure, chromosome location, and expression of the mouse zinc finger gene Krox-20: multiple gene products and coregulation with the proto-oncogene c-fos". Molecular and Cellular Biology. 9 (2): 787–97. doi:10.1128/mcb.9.2.787. PMC 362656. PMID 2496302.
- ^ a b c Swiatek PJ, Gridley T (novembar 1993). "Perinatal lethality and defects in hindbrain development in mice homozygous for a targeted mutation of the zinc finger gene Krox20". Genes & Development. 7 (11): 2071–84. doi:10.1101/gad.7.11.2071. PMID 8224839.
- ^ a b Wilkinson DG, Bhatt S, Chavrier P, Bravo R, Charnay P (februar 1989). "Segment-specific expression of a zinc-finger gene in the developing nervous system of the mouse". Nature. 337 (6206): 461–4. Bibcode:1989Natur.337..461W. doi:10.1038/337461a0. PMID 2915691. S2CID 4336310.
- ^ a b Bradley LC, Snape A, Bhatt S, Wilkinson DG (januar 1993). "The structure and expression of the Xenopus Krox-20 gene: conserved and divergent patterns of expression in rhombomeres and neural crest". Mechanisms of Development. 40 (1–2): 73–84. doi:10.1016/0925-4773(93)90089-g. PMID 8443108. S2CID 20347966.
- ^ Bhat RV, Worley PF, Cole AJ, Baraban JM (april 1992). "Activation of the zinc finger encoding gene krox-20 in adult rat brain: comparison with zif268". Brain Research. Molecular Brain Research. 13 (3): 263–6. doi:10.1016/0169-328x(92)90034-9. PMID 1317498.
- ^ Wilkinson DG, Bhatt S, Cook M, Boncinelli E, Krumlauf R (oktobar 1989). "Segmental expression of Hox-2 homoeobox-containing genes in the developing mouse hindbrain". Nature. 341 (6241): 405–9. Bibcode:1989Natur.341..405W. doi:10.1038/341405a0. PMID 2571936. S2CID 4324322.
- ^ Hunt P, Gulisano M, Cook M, Sham MH, Faiella A, Wilkinson D, Boncinelli E, Krumlauf R (oktobar 1991). "A distinct Hox code for the branchial region of the vertebrate head". Nature. 353 (6347): 861–4. Bibcode:1991Natur.353..861H. doi:10.1038/353861a0. PMID 1682814. S2CID 4312466.
- ^ Oxtoby E, Jowett T (mart 1993). "Cloning of the zebrafish krox-20 gene (krx-20) and its expression during hindbrain development". Nucleic Acids Research. 21 (5): 1087–95. doi:10.1093/nar/21.5.1087. PMC 309267. PMID 8464695.
- ^ Frohman MA, Boyle M, Martin GR (oktobar 1990). "Isolation of the mouse Hox-2.9 gene; analysis of embryonic expression suggests that positional information along the anterior-posterior axis is specified by mesoderm". Development. 110 (2): 589–607. doi:10.1242/dev.110.2.589. PMID 1983472.
- ^ Murphy P, Davidson DR, Hill RE (septembar 1989). "Segment-specific expression of a homoeobox-containing gene in the mouse hindbrain". Nature. 341 (6238): 156–9. Bibcode:1989Natur.341..156M. doi:10.1038/341156a0. PMID 2571087. S2CID 4371764.
- ^ Nieto MA, Bradley LC, Wilkinson DG (1991). "Conserved segmental expression of Krox-20 in the vertebrate hindbrain and its relationship to lineage restriction". Development. Suppl 2: 59–62. doi:10.1242/dev.113.Supplement_2.59. hdl:10261/32226. PMID 1688180.
- ^ "UniProt, P11161". Pristupljeno 1. 9. 2021.
- ^ "Entrez Gene: EGR2 early growth response 2 (Krox-20 homolog, Drosophila)".
- ^ Boerkoel CF, Takashima H, Bacino CA, Daentl D, Lupski JR (juli 2001). "EGR2 mutation R359W causes a spectrum of Dejerine-Sottas neuropathy". Neurogenetics. 3 (3): 153–7. doi:10.1007/s100480100107. PMID 11523566. S2CID 32746701.
- ^ Warner LE, Mancias P, Butler IJ, McDonald CM, Keppen L, Koob KG, Lupski JR (april 1998). "Mutations in the early growth response 2 (EGR2) gene are associated with hereditary myelinopathies". Nature Genetics. 18 (4): 382–4. doi:10.1038/ng0498-382. PMID 9537424. S2CID 25550479.
- ^ Chandra A, Lan S, Zhu J, Siclari VA, Qin L (juli 2013). "Epidermal growth factor receptor (EGFR) signaling promotes proliferation and survival in osteoprogenitors by increasing early growth response 2 (EGR2) expression". The Journal of Biological Chemistry (jezik: engleski). 288 (28): 20488–98. doi:10.1074/jbc.M112.447250. PMC 3711314. PMID 23720781.
- ^ Grünewald TG, Bernard V, Gilardi-Hebenstreit P, Raynal V, Surdez D, Aynaud MM, et al. (septembar 2015). "Chimeric EWSR1-FLI1 regulates the Ewing sarcoma susceptibility gene EGR2 via a GGAA microsatellite". Nature Genetics. 47 (9): 1073–8. doi:10.1038/ng.3363. PMC 4591073. PMID 26214589.
- ^ Le, Lu. "Scientists find skin cells at the root of balding, gray hair". UT Southwestern Medical Center. Arhivirano s originala, 9. 5. 2017. Pristupljeno 9. 5. 2017.
Dopunska literatura
uredi- Rangnekar VM, Aplin AC, Sukhatme VP (maj 1990). "The serum and TPA responsive promoter and intron-exon structure of EGR2, a human early growth response gene encoding a zinc finger protein". Nucleic Acids Research. 18 (9): 2749–57. doi:10.1093/nar/18.9.2749. PMC 330760. PMID 2111009.
- Chavrier P, Janssen-Timmen U, Mattéi MG, Zerial M, Bravo R, Charnay P (februar 1989). "Structure, chromosome location, and expression of the mouse zinc finger gene Krox-20: multiple gene products and coregulation with the proto-oncogene c-fos". Molecular and Cellular Biology. 9 (2): 787–97. doi:10.1128/mcb.9.2.787. PMC 362656. PMID 2496302.
- Joseph LJ, Le Beau MM, Jamieson GA, Acharya S, Shows TB, Rowley JD, Sukhatme VP (oktobar 1988). "Molecular cloning, sequencing, and mapping of EGR2, a human early growth response gene encoding a protein with "zinc-binding finger" structure". Proceedings of the National Academy of Sciences of the United States of America. 85 (19): 7164–8. Bibcode:1988PNAS...85.7164J. doi:10.1073/pnas.85.19.7164. PMC 282144. PMID 3140236.
- Topilko P, Schneider-Maunoury S, Levi G, Baron-Van Evercooren A, Chennoufi AB, Seitanidou T, Babinet C, Charnay P (oktobar 1994). "Krox-20 controls myelination in the peripheral nervous system". Nature. 371 (6500): 796–9. Bibcode:1994Natur.371..796T. doi:10.1038/371796a0. PMID 7935840. S2CID 4333028.
- Sham MH, Vesque C, Nonchev S, Marshall H, Frain M, Gupta RD, Whiting J, Wilkinson D, Charnay P, Krumlauf R (januar 1993). "The zinc finger gene Krox20 regulates HoxB2 (Hox2.8) during hindbrain segmentation". Cell. 72 (2): 183–96. doi:10.1016/0092-8674(93)90659-E. PMID 8093858. S2CID 3205209.
- Levi G, Topilko P, Schneider-Maunoury S, Lasagna M, Mantero S, Pesce B, Ghersi G, Cancedda R, Charnay P (juni 1996). "Role of Krox-20 in endochondral bone formation". Annals of the New York Academy of Sciences. 785 (1): 288–91. Bibcode:1996NYASA.785..288L. doi:10.1111/j.1749-6632.1996.tb56286.x. PMID 8702157. S2CID 27761983.
- Warner LE, Mancias P, Butler IJ, McDonald CM, Keppen L, Koob KG, Lupski JR (april 1998). "Mutations in the early growth response 2 (EGR2) gene are associated with hereditary myelinopathies". Nature Genetics. 18 (4): 382–4. doi:10.1038/ng0498-382. PMID 9537424. S2CID 25550479.
- Warner LE, Svaren J, Milbrandt J, Lupski JR (juli 1999). "Functional consequences of mutations in the early growth response 2 gene (EGR2) correlate with severity of human myelinopathies". Human Molecular Genetics. 8 (7): 1245–51. doi:10.1093/hmg/8.7.1245. PMID 10369870.
- Timmerman V, De Jonghe P, Ceuterick C, De Vriendt E, Löfgren A, Nelis E, Warner LE, Lupski JR, Martin JJ, Van Broeckhoven C (juni 1999). "Novel missense mutation in the early growth response 2 gene associated with Dejerine-Sottas syndrome phenotype". Neurology. 52 (9): 1827–32. doi:10.1212/wnl.52.9.1827. PMID 10371530. S2CID 11569651.
- Bellone E, Di Maria E, Soriani S, Varese A, Doria LL, Ajmar F, Mandich P (oktobar 1999). "A novel mutation (D305V) in the early growth response 2 gene is associated with severe Charcot-Marie-Tooth type 1 disease". Human Mutation. 14 (4): 353–4. doi:10.1002/(SICI)1098-1004(199910)14:4<353::AID-HUMU17>3.0.CO;2-4. PMID 10502832.
- Pareyson D, Taroni F, Botti S, Morbin M, Baratta S, Lauria G, Ciano C, Sghirlanzoni A (april 2000). "Cranial nerve involvement in CMT disease type 1 due to early growth response 2 gene mutation". Neurology. 54 (8): 1696–8. doi:10.1212/wnl.54.8.1696. hdl:2434/531868. PMID 10762521. S2CID 28404231.
- Gambardella L, Schneider-Maunoury S, Voiculescu O, Charnay P, Barrandon Y (septembar 2000). "Pattern of expression of the transcription factor Krox-20 in mouse hair follicle". Mechanisms of Development. 96 (2): 215–8. doi:10.1016/S0925-4773(00)00398-1. PMID 10960786. S2CID 18000564.
- Yoshihara T, Kanda F, Yamamoto M, Ishihara H, Misu K, Hattori N, Chihara K, Sobue G (mart 2001). "A novel missense mutation in the early growth response 2 gene associated with late-onset Charcot--Marie--Tooth disease type 1". Journal of the Neurological Sciences. 184 (2): 149–53. doi:10.1016/S0022-510X(00)00504-9. PMID 11239949. S2CID 19693658.
- Boerkoel CF, Takashima H, Bacino CA, Daentl D, Lupski JR (juli 2001). "EGR2 mutation R359W causes a spectrum of Dejerine-Sottas neuropathy". Neurogenetics. 3 (3): 153–7. doi:10.1007/s100480100107. PMID 11523566. S2CID 32746701.
- Yang Y, Dong B, Mittelstadt PR, Xiao H, Ashwell JD (maj 2002). "HIV Tat binds Egr proteins and enhances Egr-dependent transactivation of the Fas ligand promoter". The Journal of Biological Chemistry. 277 (22): 19482–7. doi:10.1074/jbc.M201687200. PMID 11909874.
- Vandenberghe N, Upadhyaya M, Gatignol A, Boutrand L, Boucherat M, Chazot G, Vandenberghe A, Latour P (decembar 2002). "Frequency of mutations in the early growth response 2 gene associated with peripheral demyelinating neuropathies". Journal of Medical Genetics. 39 (12): 81e–81. doi:10.1136/jmg.39.12.e81. PMC 1757229. PMID 12471219.
- Musso M, Balestra P, Taroni F, Bellone E, Mandich P (februar 2003). "Different consequences of EGR2 mutants on the transactivation of human Cx32 promoter". Neurobiology of Disease. 12 (1): 89–95. doi:10.1016/S0969-9961(02)00018-9. PMID 12609493. S2CID 29600641.
- Unoki M, Nakamura Y (april 2003). "EGR2 induces apoptosis in various cancer cell lines by direct transactivation of BNIP3L and BAK". Oncogene. 22 (14): 2172–85. doi:10.1038/sj.onc.1206222. PMID 12687019.
- Numakura C, Shirahata E, Yamashita S, Kanai M, Kijima K, Matsuki T, Hayasaka K (juni 2003). "Screening of the early growth response 2 gene in Japanese patients with Charcot-Marie-Tooth disease type 1". Journal of the Neurological Sciences. 210 (1–2): 61–4. doi:10.1016/S0022-510X(03)00028-5. PMID 12736090. S2CID 36723641.