Ku70

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Estrutura tridimensional da Ku70

Ku70 é uma proteína que em humanos é codificada pelo gene XRCC6.[1] Ku70 junto com Ku80, conformam um heterodimero denominado proteína Ku, que se liga as extremidades da dupla fita de DNA que foi cortado, e é requerida para o processo de recombinação não homóloga durante a reparação do DNA. Também é necessária para o processo de recombinação V(D)J, que consegue aumentar a diversidade antigênica do sistema imune de mamíferos utilizando o processo de recombinação não homóloga. Ku também é necessária para manter o tamanho do telômero e silenciamento de genes subteloméricos.

Ku foi originalmente identificado em pacientes com lúpus eritematoso sistêmico , no qual, após ser submetido a análise, eles encontraram altos níveis de autoanticorpos contra essa proteína.[1]

Outros nomes[editar | editar código-fonte]

  • Lupus Ku autoantigen protein p70
  • ATP-dependent DNA helicase 2 subunit 1
  • X-ray repair complementing defective repair in Chinese hamster cells 6
  • X-ray repair cross-complementing 6 (XRCC6)

Interações[editar | editar código-fonte]

Interage com GCN5L2,[2] PTTG1,[3] HOXC4,[4] CHEK1,[5] Werner syndrome ATP-dependent helicase,[6] [7] RPA2,[8] CBX5,[9] CREB-binding protein,[2] Neutrophil cytosolic factor 4,[10] MRE11A,[11] NCOA6,[12] [13] Ku80,[2] [14] [15] [16] [17] TERF2,[17] VAV1,[18] Telomerase reverse transcriptase[19] e PCNA.[20] [21]

Referências

  1. a b «Entrez Gene: XRCC6 X-ray repair complementing defective repair in Chinese hamster cells 6 (Ku autoantigen, 70kDa)». 
  2. a b c Barlev, N A; Poltoratsky V, Owen-Hughes T, Ying C, Liu L, Workman J L, Berger S L (1998). «Repression of GCN5 histone acetyltransferase activity via bromodomain-mediated binding and phosphorylation by the Ku-DNA-dependent protein kinase complex». Mol. Cell. Biol. (UNITED STATES [s.n.]) 18 (3): 1349–58. ISSN 0270-7306. PMC 108848. PMID 9488450. 
  3. Romero, F; Multon M C, Ramos-Morales F, Domínguez A, Bernal J A, Pintor-Toro J A, Tortolero M (2001). «Human securin, hPTTG, is associated with Ku heterodimer, the regulatory subunit of the DNA-dependent protein kinase». Nucleic Acids Res. (England [s.n.]) 29 (6): 1300–7. doi:10.1093/nar/29.6.1300. PMC 29753. PMID 11238996. 
  4. Schild-Poulter, C; Pope L, Giffin W, Kochan J C, Ngsee J K, Traykova-Andonova M, Haché R J (2001). «The binding of Ku antigen to homeodomain proteins promotes their phosphorylation by DNA-dependent protein kinase». J. Biol. Chem. (United States [s.n.]) 276 (20): 16848–56. doi:10.1074/jbc.M100768200. ISSN 0021-9258. PMID 11279128. 
  5. Goudelock, Dawn Marie; Jiang Kecheng, Pereira Elizabeth, Russell Beatriz, Sanchez Yolanda (2003). «Regulatory interactions between the checkpoint kinase Chk1 and the proteins of the DNA-dependent protein kinase complex». J. Biol. Chem. (United States [s.n.]) 278 (32): 29940–7. doi:10.1074/jbc.M301765200. ISSN 0021-9258. PMID 12756247. 
  6. Karmakar, Parimal; Snowden Carey M, Ramsden Dale A, Bohr Vilhelm A (2002). «Ku heterodimer binds to both ends of the Werner protein and functional interaction occurs at the Werner N-terminus». Nucleic Acids Res. (England [s.n.]) 30 (16): 3583–91. doi:10.1093/nar/gkf482. PMC 134248. PMID 12177300. 
  7. Li, B; Comai L (2000). «Functional interaction between Ku and the werner syndrome protein in DNA end processing». J. Biol. Chem. (UNITED STATES [s.n.]) 275 (37): 28349–52. doi:10.1074/jbc.C000289200. ISSN 0021-9258. PMID 10880505. 
  8. Shao, R G; Cao C X, Zhang H, Kohn K W, Wold M S, Pommier Y (1999). «Replication-mediated DNA damage by camptothecin induces phosphorylation of RPA by DNA-dependent protein kinase and dissociates RPA:DNA-PK complexes». EMBO J. (ENGLAND [s.n.]) 18 (5): 1397–406. doi:10.1093/emboj/18.5.1397. ISSN 0261-4189. PMC 1171229. PMID 10064605. 
  9. Song, K; Jung Y, Jung D, Lee I (2001). «Human Ku70 interacts with heterochromatin protein 1alpha». J. Biol. Chem. (United States [s.n.]) 276 (11): 8321–7. doi:10.1074/jbc.M008779200. ISSN 0021-9258. PMID 11112778. 
  10. Grandvaux, N; Grizot S, Vignais P V, Dagher M C (1999). «The Ku70 autoantigen interacts with p40phox in B lymphocytes». J. Cell. Sci. (ENGLAND [s.n.]). 112 ( Pt 4): 503–13. ISSN 0021-9533. PMID 9914162. 
  11. Goedecke, W; Eijpe M, Offenberg H H, van Aalderen M, Heyting C (1999). «Mre11 and Ku70 interact in somatic cells, but are differentially expressed in early meiosis». Nat. Genet. (UNITED STATES [s.n.]) 23 (2): 194–8. doi:10.1038/13821. ISSN 1061-4036. PMID 10508516.  Parâmetro desconhecido |DUPLICATE DATA: pmid= ignorado (Ajuda)
  12. Ko, L; Cardona G R, Chin W W (2000). «Thyroid hormone receptor-binding protein, an LXXLL motif-containing protein, functions as a general coactivator». Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES [s.n.]) 97 (11): 6212–7. doi:10.1073/pnas.97.11.6212. ISSN 0027-8424. PMC 18584. PMID 10823961. 
  13. Ko, Lan; Chin William W (2003). «Nuclear receptor coactivator thyroid hormone receptor-binding protein (TRBP) interacts with and stimulates its associated DNA-dependent protein kinase». J. Biol. Chem. (United States [s.n.]) 278 (13): 11471–9. doi:10.1074/jbc.M209723200. ISSN 0021-9258. PMID 12519782. 
  14. Gell, D; Jackson S P (1999). «Mapping of protein-protein interactions within the DNA-dependent protein kinase complex». Nucleic Acids Res. (ENGLAND [s.n.]) 27 (17): 3494–502. doi:10.1093/nar/27.17.3494. PMC 148593. PMID 10446239. 
  15. Yang, C R; Yeh S, Leskov K, Odegaard E, Hsu H L, Chang C, Kinsella T J, Chen D J, Boothman D A (1999). «Isolation of Ku70-binding proteins (KUBs)». Nucleic Acids Res. (ENGLAND [s.n.]) 27 (10): 2165–74. doi:10.1093/nar/27.10.2165. ISSN 0305-1048. PMC 148436. PMID 10219089. 
  16. Singleton, B K; Torres-Arzayus M I, Rottinghaus S T, Taccioli G E, Jeggo P A (1999). «The C terminus of Ku80 activates the DNA-dependent protein kinase catalytic subunit». Mol. Cell. Biol. (UNITED STATES [s.n.]) 19 (5): 3267–77. ISSN 0270-7306. PMC 84121. PMID 10207052. 
  17. a b Song, K; Jung D, Jung Y, Lee S G, Lee I (2000). «Interaction of human Ku70 with TRF2». FEBS Lett. (NETHERLANDS [s.n.]) 481 (1): 81–5. doi:10.1016/S0014-5793(00)01958-X. ISSN 0014-5793. PMID 10984620. 
  18. Romero, F; Dargemont C, Pozo F, Reeves W H, Camonis J, Gisselbrecht S, Fischer S (1996). «p95vav associates with the nuclear protein Ku-70». Mol. Cell. Biol. (UNITED STATES [s.n.]) 16 (1): 37–44. ISSN 0270-7306. PMC 230976. PMID 8524317. 
  19. Chai, Weihang; Ford Lance P, Lenertz Lisa, Wright Woodring E, Shay Jerry W (2002). «Human Ku70/80 associates physically with telomerase through interaction with hTERT». J. Biol. Chem. (United States [s.n.]) 277 (49): 47242–7. doi:10.1074/jbc.M208542200. ISSN 0021-9258. PMID 12377759. 
  20. Ohta, Satoshi; Shiomi Yasushi, Sugimoto Katsunori, Obuse Chikashi, Tsurimoto Toshiki (2002). «A proteomics approach to identify proliferating cell nuclear antigen (PCNA)-binding proteins in human cell lysates. Identification of the human CHL12/RFCs2-5 complex as a novel PCNA-binding protein». J. Biol. Chem. (United States [s.n.]) 277 (43): 40362–7. doi:10.1074/jbc.M206194200. ISSN 0021-9258. PMID 12171929. 
  21. Balajee, A S; Geard C R (2001). «Chromatin-bound PCNA complex formation triggered by DNA damage occurs independent of the ATM gene product in human cells». Nucleic Acids Res. (England [s.n.]) 29 (6): 1341–51. doi:10.1093/nar/29.6.1341. PMC 29758. PMID 11239001.