Promyelocytic leukemia protein

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Promyelocytic leukemia
Protein PML PDB 1bor.png
PDB rendering based on 1bor.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols PML ; MYL; PP8675; RNF71; TRIM19
External IDs OMIM102578 MGI104662 HomoloGene13245 GeneCards: PML Gene
Orthologs
Species Human Mouse
Entrez 5371 18854
Ensembl ENSG00000140464 ENSMUSG00000036986
UniProt P29590 Q60953
RefSeq (mRNA) NM_002675 NM_008884
RefSeq (protein) NP_002666 NP_032910
Location (UCSC) Chr 15:
74.29 – 74.34 Mb
Chr 9:
58.22 – 58.25 Mb
PubMed search [1] [2]

Probable transcription factor PML is a tumor suppressor protein that in humans is encoded by the PML gene.

Function[edit]

The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. This phosphoprotein localizes to nuclear bodies (Nuclear dots) where it functions as a transcription factor and tumor suppressor. Its expression is cell-cycle related and it regulates the p53 response to oncogenic signals. The gene is often involved in the translocation with the retinoic acid receptor alpha gene associated with acute promyelocytic leukemia (APL). Extensive alternative splicing of this gene results in several variations of the protein's central and C-terminal regions; all variants encode the same N-terminus. Alternatively spliced transcript variants encoding different isoforms have been identified.[1]

Interactions[edit]

Promyelocytic leukemia protein has been shown to interact with:

See also[edit]

References[edit]

  1. ^ "Entrez Gene: PML promyelocytic leukemia". 
  2. ^ Kojic S, Medeot E, Guccione E, Krmac H, Zara I, Martinelli V et al. (May 2004). "The Ankrd2 protein, a link between the sarcomere and the nucleus in skeletal muscle". J. Mol. Biol. 339 (2): 313–25. doi:10.1016/j.jmb.2004.03.071. PMID 15136035. 
  3. ^ a b Zhong S, Delva L, Rachez C, Cenciarelli C, Gandini D, Zhang H et al. (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. doi:10.1038/15463. PMID 10610177. 
  4. ^ a b Matsuzaki K, Minami T, Tojo M, Honda Y, Saitoh N, Nagahiro S et al. (Mar 2003). "PML-nuclear bodies are involved in cellular serum response". Genes Cells 8 (3): 275–86. PMID 12622724. 
  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. 
  6. ^ Marcello A, Ferrari A, Pellegrini V, Pegoraro G, Lusic M, Beltram F et al. (May 2003). "Recruitment of human cyclin T1 to nuclear bodies through direct interaction with the PML protein". EMBO J. 22 (9): 2156–66. doi:10.1093/emboj/cdg205. PMC 156077. PMID 12727882. 
  7. ^ Ishov AM, Sotnikov AG, Negorev D, Vladimirova OV, Neff N, Kamitani T et al. (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. 
  8. ^ Li H, Leo C, Zhu J, Wu X, O'Neil J, Park EJ et al. (Mar 2000). "Sequestration and inhibition of Daxx-mediated transcriptional repression by PML". Mol. Cell. Biol. 20 (5): 1784–96. PMC 85360. PMID 10669754. 
  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. doi:10.1038/sj.onc.1204063. PMID 11244500. 
  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. 
  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. 
  12. ^ a b c d e Khan MM, Nomura T, Kim H, Kaul SC, Wadhwa R, Shinagawa T et al. (Jun 2001). "Role of PML and PML-RARalpha in Mad-mediated transcriptional repression". Mol. Cell 7 (6): 1233–43. PMID 11430826. 
  13. ^ a b Wu WS, Vallian S, Seto E, Yang WM, Edmondson D, Roth S et al. (Apr 2001). "The growth suppressor PML represses transcription by functionally and physically interacting with histone deacetylases". Mol. Cell. Biol. 21 (7): 2259–68. doi:10.1128/MCB.21.7.2259-2268.2001. PMC 86860. PMID 11259576. 
  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. doi:10.1038/sj.onc.1203201. PMID 10597310. 
  15. ^ Shin J, Park B, Cho S, Lee S, Kim Y, Lee SO et al. (Sep 2004). "Promyelocytic leukemia is a direct inhibitor of SAPK2/p38 mitogen-activated protein kinase". J. Biol. Chem. 279 (39): 40994–1003. doi:10.1074/jbc.M407369200. PMID 15273249. 
  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. doi:10.1016/j.yexcr.2004.03.014. PMID 15194430. 
  17. ^ a b 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. doi:10.1242/jcs.00714. PMID 12915590. 
  18. ^ a b 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. doi:10.1038/ncb1147. PMID 15195100. 
  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. doi:10.1074/jbc.M308302200. PMID 14507915. 
  20. ^ Wei X, Yu ZK, Ramalingam A, Grossman SR, Yu JH, Bloch DB et al. (Aug 2003). "Physical and functional interactions between PML and MDM2". J. Biol. Chem. 278 (31): 29288–97. doi:10.1074/jbc.M212215200. PMID 12759344. 
  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. doi:10.1038/sj.onc.1205491. PMID 12032831. 
  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. doi:10.1128/MCB.21.21.7172-7182.2001. PMC 99892. PMID 11585900. 
  23. ^ Fogal V, Gostissa M, Sandy P, Zacchi P, Sternsdorf T, Jensen K et al. (Nov 2000). "Regulation of p53 activity in nuclear bodies by a specific PML isoform". EMBO J. 19 (22): 6185–95. doi:10.1093/emboj/19.22.6185. PMC 305840. PMID 11080164. 
  24. ^ Guo A, Salomoni P, Luo J, Shih A, Zhong S, Gu W et al. (Oct 2000). "The function of PML in p53-dependent apoptosis". Nat. Cell Biol. 2 (10): 730–6. doi:10.1038/35036365. PMID 11025664. 
  25. ^ Alcalay M, Tomassoni L, Colombo E, Stoldt S, Grignani F, Fagioli M et al. (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. doi:10.1182/blood-2002-08-2474. PMID 12506013. 
  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. doi:10.1074/jbc.M200633200. PMID 11948183. 
  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. 
  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. 
  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. doi:10.1074/jbc.M408130200. PMID 15569683. 
  32. ^ Koken MH, Reid A, Quignon F, Chelbi-Alix MK, Davies JM, Kabarowski JH et al. (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. 

Further reading[edit]

External links[edit]