Proteína da leucemia promielocítica

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Protein PML PDB 1bor.png
PDB 1bor
Proteína da leucemia promielocítica
Identificadores
Símbolo PML
Símbolos alt. MYL; PP8675; RNF71; TRIM19
Entrez 5371
OMIM 102578
RefSeq NP_002666
UniProt P29590
Outros datos
Locus Cr. 15 :(74.29 – 74.34 Mb)

A proteína da leucemia promielocítica é unha proteína supresora de tumores que nos humanos está codificada no xene PML do cromosoma 15.

Función[editar | editar a fonte]

A proteína codificada por este xene é membro da familia do motivo tripartiro (TRIM). O motivo TRIM inclúe tres dominios de unión ao zinc, un RING, unha caixa B tipo 1 e unha caixa B tipo 2, e unha rexión de hélice superenrolada (coiled-coil). É unha fosfoproteína que se localiza nos corpos nucleares (puntos nucleares ou corpos PML), onde funciona como factor de transcrición e supresor de tumores. A súa expresión está relacionada co ciclo celular e regula a resposta p53 a sinais oncoxénicos. O xene está a miúdo implicado na translocación co xene alfa do receptor de ácido retinoico asociado coa leucemia promielocítica aguda. O amplo splicing alternativo deste xene orixina diversas variacións das rexións central e C-terminal da proteína, pero todas as variantes codifican o mesmo N-terminal. Identificáronse variantes de transcrición de splicing alternativo que codifican distintas isoformas.[1]

Interaccións[editar | editar a fonte]

A proteína da leucemia promielocítica presenta interaccións con:

Notas[editar | editar a fonte]

  1. "Entrez Gene: PML promyelocytic leukemia". 
  2. Kojic S, Medeot E, Guccione E, Krmac H, Zara I, Martinelli V, Valle G, Faulkner G (May 2004). "The Ankrd2 protein, a link between the sarcomere and the nucleus in skeletal muscle". J. Mol. Biol. 339 (2): 313–25. PMID 15136035. doi:10.1016/j.jmb.2004.03.071. 
  3. 3,0 3,1 Zhong S, Delva L, Rachez C, Cenciarelli C, Gandini D, Zhang H, Kalantry S, Freedman LP, Pandolfi PP (Nov 1999). "A RA-dependent, tumour-growth suppressive transcription complex is the target of the PML-RARalpha and T18 oncoproteins". Nat. Genet. 23 (3): 287–95. PMID 10610177. doi:10.1038/15463. 
  4. 4,0 4,1 Matsuzaki K, Minami T, Tojo M, Honda Y, Saitoh N, Nagahiro S, Saya H, Nakao M (Mar 2003). "PML-nuclear bodies are involved in cellular serum response". Genes Cells 8 (3): 275–86. PMID 12622724. doi:10.1046/j.1365-2443.2003.00632.x. 
  5. Doucas V, Tini M, Egan DA, Evans RM (Mar 1999). "Modulation of CREB binding protein function by the promyelocytic (PML) oncoprotein suggests a role for nuclear bodies in hormone signaling". Proc. Natl. Acad. Sci. U.S.A. 96 (6): 2627–32. PMC 15819. PMID 10077561. doi:10.1073/pnas.96.6.2627. 
  6. Marcello A, Ferrari A, Pellegrini V, Pegoraro G, Lusic M, Beltram F, Giacca M (May 2003). "Recruitment of human cyclin T1 to nuclear bodies through direct interaction with the PML protein". EMBO J. 22 (9): 2156–66. PMC 156077. PMID 12727882. doi:10.1093/emboj/cdg205. 
  7. Ishov AM, Sotnikov AG, Negorev D, Vladimirova OV, Neff N, Kamitani T, Yeh ET, Strauss JF, Maul GG (Oct 1999). "PML is critical for ND10 formation and recruits the PML-interacting protein daxx to this nuclear structure when modified by SUMO-1". J. Cell Biol. 147 (2): 221–34. PMC 2174231. PMID 10525530. doi:10.1083/jcb.147.2.221. 
  8. Li H, Leo C, Zhu J, Wu X, O'Neil J, Park EJ, Chen JD (Mar 2000). "Sequestration and inhibition of Daxx-mediated transcriptional repression by PML". Mol. Cell. Biol. 20 (5): 1784–96. PMC 85360. PMID 10669754. doi:10.1128/mcb.20.5.1784-1796.2000. 
  9. Lehembre F, Müller S, Pandolfi PP, Dejean A (Jan 2001). "Regulation of Pax3 transcriptional activity by SUMO-1-modified PML". Oncogene 20 (1): 1–9. PMID 11244500. doi:10.1038/sj.onc.1204063. 
  10. Zhong S, Salomoni P, Ronchetti S, Guo A, Ruggero D, Pandolfi PP (Feb 2000). "Promyelocytic leukemia protein (PML) and Daxx participate in a novel nuclear pathway for apoptosis". J. Exp. Med. 191 (4): 631–40. PMC 2195846. PMID 10684855. doi:10.1084/jem.191.4.631. 
  11. Tsuzuki S, Towatari M, Saito H, Enver T (Sep 2000). "Potentiation of GATA-2 activity through interactions with the promyelocytic leukemia protein (PML) and the t(15;17)-generated PML-retinoic acid receptor alpha oncoprotein". Mol. Cell. Biol. 20 (17): 6276–86. PMC 86102. PMID 10938104. doi:10.1128/mcb.20.17.6276-6286.2000. 
  12. 12,0 12,1 12,2 12,3 12,4 Khan MM, Nomura T, Kim H, Kaul SC, Wadhwa R, Shinagawa T, Ichikawa-Iwata E, Zhong S, Pandolfi PP, Ishii S (Jun 2001). "Role of PML and PML-RARalpha in Mad-mediated transcriptional repression". Mol. Cell 7 (6): 1233–43. PMID 11430826. doi:10.1016/s1097-2765(01)00257-x. 
  13. 13,0 13,1 Wu WS, Vallian S, Seto E, Yang WM, Edmondson D, Roth S, Chang KS (Apr 2001). "The growth suppressor PML represses transcription by functionally and physically interacting with histone deacetylases". Mol. Cell. Biol. 21 (7): 2259–68. PMC 86860. PMID 11259576. doi:10.1128/MCB.21.7.2259-2268.2001. 
  14. Topcu Z, Mack DL, Hromas RA, Borden KL (Nov 1999). "The promyelocytic leukemia protein PML interacts with the proline-rich homeodomain protein PRH: a RING may link hematopoiesis and growth control". Oncogene 18 (50): 7091–100. PMID 10597310. doi:10.1038/sj.onc.1203201. 
  15. Shin J, Park B, Cho S, Lee S, Kim Y, Lee SO, Cho K, Lee S, Jin BS, Ahn JH, Choi EJ, Ahn K (Sep 2004). "Promyelocytic leukemia is a direct inhibitor of SAPK2/p38 mitogen-activated protein kinase". J. Biol. Chem. 279 (39): 40994–1003. PMID 15273249. doi:10.1074/jbc.M407369200. 
  16. Dahle Ø, Bakke O, Gabrielsen OS (Jul 2004). "c-Myb associates with PML in nuclear bodies in hematopoietic cells". Exp. Cell Res. 297 (1): 118–26. PMID 15194430. doi:10.1016/j.yexcr.2004.03.014. 
  17. 17,0 17,1 Kurki S, Latonen L, Laiho M (Oct 2003). "Cellular stress and DNA damage invoke temporally distinct Mdm2, p53 and PML complexes and damage-specific nuclear relocalization". J. Cell. Sci. 116 (Pt 19): 3917–25. PMID 12915590. doi:10.1242/jcs.00714. 
  18. 18,0 18,1 Bernardi R, Scaglioni PP, Bergmann S, Horn HF, Vousden KH, Pandolfi PP (Jul 2004). "PML regulates p53 stability by sequestering Mdm2 to the nucleolus". Nat. Cell Biol. 6 (7): 665–72. PMID 15195100. doi:10.1038/ncb1147. 
  19. Zhu H, Wu L, Maki CG (Dec 2003). "MDM2 and promyelocytic leukemia antagonize each other through their direct interaction with p53". J. Biol. Chem. 278 (49): 49286–92. PMID 14507915. doi:10.1074/jbc.M308302200. 
  20. Wei X, Yu ZK, Ramalingam A, Grossman SR, Yu JH, Bloch DB, Maki CG (Aug 2003). "Physical and functional interactions between PML and MDM2". J. Biol. Chem. 278 (31): 29288–97. PMID 12759344. doi:10.1074/jbc.M212215200. 
  21. Wu WS, Xu ZX, Ran R, Meng F, Chang KS (May 2002). "Promyelocytic leukemia protein PML inhibits Nur77-mediated transcription through specific functional interactions". Oncogene 21 (24): 3925–33. PMID 12032831. doi:10.1038/sj.onc.1205491. 
  22. Hong SH, Yang Z, Privalsky ML (Nov 2001). "Arsenic trioxide is a potent inhibitor of the interaction of SMRT corepressor with Its transcription factor partners, including the PML-retinoic acid receptor alpha oncoprotein found in human acute promyelocytic leukemia". Mol. Cell. Biol. 21 (21): 7172–82. PMC 99892. PMID 11585900. doi:10.1128/MCB.21.21.7172-7182.2001. 
  23. Fogal V, Gostissa M, Sandy P, Zacchi P, Sternsdorf T, Jensen K, Pandolfi PP, Will H, Schneider C, Del Sal G (Nov 2000). "Regulation of p53 activity in nuclear bodies by a specific PML isoform". EMBO J. 19 (22): 6185–95. PMC 305840. PMID 11080164. doi:10.1093/emboj/19.22.6185. 
  24. Guo A, Salomoni P, Luo J, Shih A, Zhong S, Gu W, Pandolfi PP (Oct 2000). "The function of PML in p53-dependent apoptosis". Nat. Cell Biol. 2 (10): 730–6. PMID 11025664. doi:10.1038/35036365. 
  25. Alcalay M, Tomassoni L, Colombo E, Stoldt S, Grignani F, Fagioli M, Szekely L, Helin K, Pelicci PG (Feb 1998). "The promyelocytic leukemia gene product (PML) forms stable complexes with the retinoblastoma protein". Mol. Cell. Biol. 18 (2): 1084–93. PMC 108821. PMID 9448006. 
  26. Kawasaki A, Matsumura I, Kataoka Y, Takigawa E, Nakajima K, Kanakura Y (May 2003). "Opposing effects of PML and PML/RAR alpha on STAT3 activity". Blood 101 (9): 3668–73. PMID 12506013. doi:10.1182/blood-2002-08-2474. 
  27. Lin DY, Shih HM (Jul 2002). "Essential role of the 58-kDa microspherule protein in the modulation of Daxx-dependent transcriptional repression as revealed by nucleolar sequestration". J. Biol. Chem. 277 (28): 25446–56. PMID 11948183. doi:10.1074/jbc.M200633200. 
  28. Kamitani T, Nguyen HP, Kito K, Fukuda-Kamitani T, Yeh ET (Feb 1998). "Covalent modification of PML by the sentrin family of ubiquitin-like proteins". J. Biol. Chem. 273 (6): 3117–20. PMID 9452416. doi:10.1074/jbc.273.6.3117. 
  29. Vallian S, Chin KV, Chang KS (Dec 1998). "The promyelocytic leukemia protein interacts with Sp1 and inhibits its transactivation of the epidermal growth factor receptor promoter". Mol. Cell. Biol. 18 (12): 7147–56. PMC 109296. PMID 9819401. 
  30. Xu ZX, Timanova-Atanasova A, Zhao RX, Chang KS (Jun 2003). "PML colocalizes with and stabilizes the DNA damage response protein TopBP1". Mol. Cell. Biol. 23 (12): 4247–56. PMC 156140. PMID 12773567. doi:10.1128/mcb.23.12.4247-4256.2003. 
  31. Takahashi H, Hatakeyama S, Saitoh H, Nakayama KI (Feb 2005). "Noncovalent SUMO-1 binding activity of thymine DNA glycosylase (TDG) is required for its SUMO-1 modification and colocalization with the promyelocytic leukemia protein". J. Biol. Chem. 280 (7): 5611–21. PMID 15569683. doi:10.1074/jbc.M408130200. 
  32. Koken MH, Reid A, Quignon F, Chelbi-Alix MK, Davies JM, Kabarowski JH, Zhu J, Dong S, Chen S, Chen Z, Tan CC, Licht J, Waxman S, de Thé H, Zelent A (Sep 1997). "Leukemia-associated retinoic acid receptor alpha fusion partners, PML and PLZF, heterodimerize and colocalize to nuclear bodies". Proc. Natl. Acad. Sci. U.S.A. 94 (19): 10255–60. PMC 23349. PMID 9294197. doi:10.1073/pnas.94.19.10255. 

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Outros artigos[editar | editar a fonte]

Bibliografía[editar | editar a fonte]

Ligazóns externas[editar | editar a fonte]