Ku70

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Estrutura tridimencional 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 auto-anticorpos 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. (Mar. 1998). "Repression of GCN5 histone acetyltransferase activity via bromodomain-mediated binding and phosphorylation by the Ku-DNA-dependent protein kinase complex". Mol. Cell. Biol. 18 (3): 1349–58 pp.. ISSN 0270-7306. PMID 9488450.
  3. Romero, F; Multon M C, Ramos-Morales F, Domínguez A, Bernal J A, Pintor-Toro J A, Tortolero M. (Mar. 2001). "Human securin, hPTTG, is associated with Ku heterodimer, the regulatory subunit of the DNA-dependent protein kinase". Nucleic Acids Res. 29 (6): 1300–7 pp.. DOI:10.1093/nar/29.6.1300. PMID 11238996.
  4. Schild-Poulter, C; Pope L, Giffin W, Kochan J C, Ngsee J K, Traykova-Andonova M, Haché R J. (May. 2001). "The binding of Ku antigen to homeodomain proteins promotes their phosphorylation by DNA-dependent protein kinase". J. Biol. Chem. 276 (20): 16848–56 pp.. DOI:10.1074/jbc.M100768200. ISSN 0021-9258. PMID 11279128.
  5. Goudelock, Dawn Marie; Jiang Kecheng, Pereira Elizabeth, Russell Beatriz, Sanchez Yolanda. (Aug. 2003). "Regulatory interactions between the checkpoint kinase Chk1 and the proteins of the DNA-dependent protein kinase complex". J. Biol. Chem. 278 (32): 29940–7 pp.. DOI:10.1074/jbc.M301765200. ISSN 0021-9258. PMID 12756247.
  6. Karmakar, Parimal; Snowden Carey M, Ramsden Dale A, Bohr Vilhelm A. (Aug. 2002). "Ku heterodimer binds to both ends of the Werner protein and functional interaction occurs at the Werner N-terminus". Nucleic Acids Res. 30 (16): 3583–91 pp.. DOI:10.1093/nar/gkf482. PMID 12177300.
  7. Li, B; Comai L. (Sep. 2000). "Functional interaction between Ku and the werner syndrome protein in DNA end processing". J. Biol. Chem. 275 (37): 28349–52 pp.. 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. (Mar. 1999). "Replication-mediated DNA damage by camptothecin induces phosphorylation of RPA by DNA-dependent protein kinase and dissociates RPA:DNA-PK complexes". EMBO J. 18 (5): 1397–406 pp.. DOI:10.1093/emboj/18.5.1397. ISSN 0261-4189. PMID 10064605.
  9. Song, K; Jung Y, Jung D, Lee I. (Mar. 2001). "Human Ku70 interacts with heterochromatin protein 1alpha". J. Biol. Chem. 276 (11): 8321–7 pp.. DOI:10.1074/jbc.M008779200. ISSN 0021-9258. PMID 11112778.
  10. Grandvaux, N; Grizot S, Vignais P V, Dagher M C. (Feb. 1999). "The Ku70 autoantigen interacts with p40phox in B lymphocytes". J. Cell. Sci. 112 ( Pt 4): 503–13 pp.. ISSN 0021-9533. PMID 9914162.
  11. Goedecke, W; Eijpe M, Offenberg H H, van Aalderen M, Heyting C. (Oct. 1999). "Mre11 and Ku70 interact in somatic cells, but are differentially expressed in early meiosis". Nat. Genet. 23 (2): 194–8 pp.. DOI:10.1038/13821. ISSN 1061-4036. PMID 10508516.
  12. Ko, L; Cardona G R, Chin W W. (May. 2000). "Thyroid hormone receptor-binding protein, an LXXLL motif-containing protein, functions as a general coactivator". Proc. Natl. Acad. Sci. U.S.A. 97 (11): 6212–7 pp.. DOI:10.1073/pnas.97.11.6212. ISSN 0027-8424. PMID 10823961.
  13. Ko, Lan; Chin William W. (Mar. 2003). "Nuclear receptor coactivator thyroid hormone receptor-binding protein (TRBP) interacts with and stimulates its associated DNA-dependent protein kinase". J. Biol. Chem. 278 (13): 11471–9 pp.. DOI:10.1074/jbc.M209723200. ISSN 0021-9258. PMID 12519782.
  14. Gell, D; Jackson S P. (Sep. 1999). "Mapping of protein-protein interactions within the DNA-dependent protein kinase complex". Nucleic Acids Res. 27 (17): 3494–502 pp.. DOI:10.1093/nar/27.17.3494. 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. (May. 1999). "Isolation of Ku70-binding proteins (KUBs)". Nucleic Acids Res. 27 (10): 2165–74 pp.. DOI:10.1093/nar/27.10.2165. ISSN 0305-1048. PMID 10219089.
  16. Singleton, B K; Torres-Arzayus M I, Rottinghaus S T, Taccioli G E, Jeggo P A. (May. 1999). "The C terminus of Ku80 activates the DNA-dependent protein kinase catalytic subunit". Mol. Cell. Biol. 19 (5): 3267–77 pp.. ISSN 0270-7306. PMID 10207052.
  17. a b Song, K; Jung D, Jung Y, Lee S G, Lee I. (Sep. 2000). "Interaction of human Ku70 with TRF2". FEBS Lett. 481 (1): 81–5 pp.. 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. (Jan. 1996). "p95vav associates with the nuclear protein Ku-70". Mol. Cell. Biol. 16 (1): 37–44 pp.. ISSN 0270-7306. PMID 8524317.
  19. Chai, Weihang; Ford Lance P, Lenertz Lisa, Wright Woodring E, Shay Jerry W. (Dec. 2002). "Human Ku70/80 associates physically with telomerase through interaction with hTERT". J. Biol. Chem. 277 (49): 47242–7 pp.. DOI:10.1074/jbc.M208542200. ISSN 0021-9258. PMID 12377759.
  20. Ohta, Satoshi; Shiomi Yasushi, Sugimoto Katsunori, Obuse Chikashi, Tsurimoto Toshiki. (Oct. 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. 277 (43): 40362–7 pp.. DOI:10.1074/jbc.M206194200. ISSN 0021-9258. PMID 12171929.
  21. Balajee, A S; Geard C R. (Mar. 2001). "Chromatin-bound PCNA complex formation triggered by DNA damage occurs independent of the ATM gene product in human cells". Nucleic Acids Res. 29 (6): 1341–51 pp.. DOI:10.1093/nar/29.6.1341. PMID 11239001.