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Promyelocytic leukemia protein

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Title: Promyelocytic leukemia protein  
Author: World Heritage Encyclopedia
Language: English
Subject: Retinoic acid receptor alpha, HHEX, MAPK11, GATA2, SIN3A
Collection: Ring Finger Proteins
Publisher: World Heritage Encyclopedia

Promyelocytic leukemia protein

Promyelocytic leukemia

PDB rendering based on 1bor.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols  ; MYL; PP8675; RNF71; TRIM19
External IDs GeneCards:
Species Human Mouse
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
PubMed search

Probable transcription factor PML is a tumor suppressor protein that in humans is encoded by the PML gene. 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 1
  • See also 2
  • References 3
  • Further reading 4
  • External links 5


Promyelocytic leukemia protein has been shown to interact with Retinoic acid receptor alpha,[2] HDAC1,[3][4] Nerve Growth factor IB,[5] SKI protein,[3] Zinc finger and BTB domain-containing protein 16,[6] Cyclin T1,[7] SIN3A,[3] Retinoblastoma protein,[8] Death associated protein 6,[9][10][11][12] STAT3,[13] CREB-binding protein,[2][14][15] Sp1 transcription factor,[16] ANKRD2,[17] Thymine-DNA glycosylase,[18] TOPBP1,[19] HHEX,[20] MAPK11,[21] Nuclear receptor co-repressor 1,[3] Nuclear receptor co-repressor 2,[3][22] P53,[23][24][25] MYB,[26] HDAC3,[4] GATA2,[27] RPL11,[28] Mdm2,[23][28][29][30] Serum response factor[14] and Small ubiquitin-related modifier 1.[31][32]

See also


  1. ^ "Entrez Gene: PML promyelocytic leukemia". 
  2. ^ a b Zhong, S; Delva L; Rachez C; Cenciarelli C; Gandini D; Zhang H; Kalantry S; Freedman L P; Pandolfi P P (Nov 1999). "A RA-dependent, tumour-growth suppressive transcription complex is the target of the PML-RARalpha and T18 oncoproteins". Nat. Genet. (UNITED STATES) 23 (3): 287–95.  
  3. ^ a b c d e Khan, M M; Nomura T; Kim H; Kaul S C; Wadhwa R; Shinagawa T; Ichikawa-Iwata E; Zhong S; Pandolfi P P; Ishii S (Jun 2001). "Role of PML and PML-RARalpha in Mad-mediated transcriptional repression". Mol. Cell (United States) 7 (6): 1233–43.  
  4. ^ a b Wu, W S; Vallian S; Seto E; Yang W M; Edmondson D; Roth S; Chang K S (Apr 2001). "The Growth Suppressor PML Represses Transcription by Functionally and Physically Interacting with Histone Deacetylases". Mol. Cell. Biol. (United States) 21 (7): 2259–68.  
  5. ^ Wu, Wen-Shu; Xu Zhi-Xiang; Ran Ruixiang; Meng Feng; Chang Kun-Sang (May 2002). "Promyelocytic leukemia protein PML inhibits Nur77-mediated transcription through specific functional interactions". Oncogene (England) 21 (24): 3925–33.  
  6. ^ Koken, M H; Reid A, Quignon F, Chelbi-Alix M K, Davies J M, Kabarowski J H, Zhu J, Dong S, Chen S, Chen Z, Tan C C, Licht J, Waxman S, de Thé H, Zelent A (Sep 1997). "Leukemia-associated retinoic acid receptor α fusion partners, PML and PLZF, heterodimerize and colocalize to nuclear bodies".  
  7. ^ Marcello, Alessandro; Ferrari Aldo; Pellegrini Vittorio; Pegoraro Gianluca; Lusic Marina; Beltram Fabio; Giacca Mauro (May 2003). "Recruitment of human cyclin T1 to nuclear bodies through direct interaction with the PML protein". EMBO J. (England) 22 (9): 2156–66.  
  8. ^ Alcalay, M; Tomassoni L; Colombo E; Stoldt S; Grignani F; Fagioli M; Szekely L; Helin K; Pelicci P G (Feb 1998). "The Promyelocytic Leukemia Gene Product (PML) Forms Stable Complexes with the Retinoblastoma Protein". Mol. Cell. Biol. (UNITED STATES) 18 (2): 1084–93.  
  9. ^ Ishov, A M; Sotnikov A G; Negorev D; Vladimirova O V; Neff N; Kamitani T; Yeh E T; Strauss J F; Maul G G (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. (UNITED STATES) 147 (2): 221–34.  
  10. ^ Li, H; Leo C; Zhu J; Wu X; O'Neil J; Park E J; Chen J D (Mar 2000). "Sequestration and Inhibition of Daxx-Mediated Transcriptional Repression by PML". Mol. Cell. Biol. (UNITED STATES) 20 (5): 1784–96.  
  11. ^ Lehembre, F; Müller S; Pandolfi P P; Dejean A (Jan 2001). "Regulation of Pax3 transcriptional activity by SUMO-1-modified PML". Oncogene (England) 20 (1): 1–9.  
  12. ^ Zhong, S; Salomoni P; Ronchetti S; Guo A; Ruggero D; Pandolfi P P (Feb 2000). "Promyelocytic Leukemia Protein (Pml) and Daxx Participate in a Novel Nuclear Pathway for Apoptosis". J. Exp. Med. (UNITED STATES) 191 (4): 631–40.  
  13. ^ Kawasaki, Akira; Matsumura Itaru; Kataoka Yoshihisa; Takigawa Eri; Nakajima Koichi; Kanakura Yuzuru (May 2003). "Opposing effects of PML and PML/RAR alpha on STAT3 activity". Blood (United States) 101 (9): 3668–73.  
  14. ^ a b Matsuzaki, Kazuhito; Minami Takeshi; Tojo Masahide; Honda Yoshiomi; Saitoh Noriko; Nagahiro Shinji; Saya Hideyuki; Nakao Mitsuyoshi (Mar 2003). "PML-nuclear bodies are involved in cellular serum response". Genes Cells (England) 8 (3): 275–86.  
  15. ^ Doucas, V; Tini M; Egan D A; Evans R M (Mar 1999). "Modulation of CREB binding protein function by the promyelocytic (PML) oncoprotein suggests a role for nuclear bodies in hormone signaling".  
  16. ^ Vallian, S; Chin K V; Chang K S (Dec 1998). "The Promyelocytic Leukemia Protein Interacts with Sp1 and Inhibits Its Transactivation of the Epidermal Growth Factor Receptor Promoter". Mol. Cell. Biol. (UNITED STATES) 18 (12): 7147–56.  
  17. ^ Kojic, Snezana; Medeot Elisa; Guccione Ernesto; Krmac Helena; Zara Ivano; Martinelli Valentina; Valle Giorgio; Faulkner Georgine (May 2004). "The Ankrd2 protein, a link between the sarcomere and the nucleus in skeletal muscle". J. Mol. Biol. (England) 339 (2): 313–25.  
  18. ^ Takahashi, Hidehisa; Hatakeyama Shigetsugu; Saitoh Hisato; Nakayama Keiichi I (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. (United States) 280 (7): 5611–21.  
  19. ^ Xu, Zhi-Xiang; Timanova-Atanasova Anna, Zhao Rui-Xun, Chang Kun-Sang (Jun 2003). "PML Colocalizes with and Stabilizes the DNA Damage Response Protein TopBP1". Mol. Cell. Biol. (United States) 23 (12): 4247–56.  
  20. ^ Topcu, Z; Mack D L; Hromas R A; Borden K L (Nov 1999). "The promyelocytic leukemia protein PML interacts with the proline-rich homeodomain protein PRH: a RING may link hematopoiesis and growth control". Oncogene (ENGLAND) 18 (50): 7091–100.  
  21. ^ Shin, Jinwook; Park Boyoun, Cho Sunglim, Lee Sunray, Kim Youngkyun, Lee Seong-Ok, Cho Kwangmin, Lee Sungwook, Jin Bong-Suk, Ahn Jin-Hyun, Choi Eui-Ju, Ahn Kwangseog (Sep 2004). "Promyelocytic leukemia is a direct inhibitor of SAPK2/p38 mitogen-activated protein kinase". J. Biol. Chem. (United States) 279 (39): 40994–1003.  
  22. ^ Hong, S H; Yang Z; Privalsky M L (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 α Oncoprotein Found in Human Acute Promyelocytic Leukemia". Mol. Cell. Biol. (United States) 21 (21): 7172–82.  
  23. ^ a b Kurki, Sari; Latonen Leena; Laiho Marikki (Oct 2003). "Cellular stress and DNA damage invoke temporally distinct Mdm2, p53 and PML complexes and damage-specific nuclear relocalization". J. Cell. Sci. (England) 116 (Pt 19): 3917–25.  
  24. ^ Fogal, V; Gostissa M; Sandy P; Zacchi P; Sternsdorf T; Jensen K; Pandolfi P P; Will H; Schneider C; Del Sal G (Nov 2000). "Regulation of p53 activity in nuclear bodies by a specific PML isoform". EMBO J. (ENGLAND) 19 (22): 6185–95.  
  25. ^ Guo, A; Salomoni P; Luo J; Shih A; Zhong S; Gu W; Pandolfi P P (Oct 2000). "The function of PML in p53-dependent apoptosis". Nat. Cell Biol. (ENGLAND) 2 (10): 730–6.  
  26. ^ Dahle, Øyvind; Bakke Oddmund; Gabrielsen Odd Stokke (Jul 2004). "c-Myb associates with PML in nuclear bodies in hematopoietic cells". Exp. Cell Res. (United States) 297 (1): 118–26.  
  27. ^ 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 α Oncoprotein". Mol. Cell. Biol. (UNITED STATES) 20 (17): 6276–86.  
  28. ^ a b Bernardi, Rosa; Scaglioni Pier Paolo; Bergmann Stephan; Horn Henning F; Vousden Karen H; Pandolfi Pier Paolo (Jul 2004). "PML regulates p53 stability by sequestering Mdm2 to the nucleolus". Nat. Cell Biol. (England) 6 (7): 665–72.  
  29. ^ Zhu, Hongyan; Wu Liqing; Maki Carl G (Dec 2003). "MDM2 and promyelocytic leukemia antagonize each other through their direct interaction with p53". J. Biol. Chem. (United States) 278 (49): 49286–92.  
  30. ^ Wei, Xiaolong; Yu Zhong Kang; Ramalingam Arivudainambi; Grossman Steven R; Yu Jiang H; Bloch Donald B; Maki Carl G (Aug 2003). "Physical and functional interactions between PML and MDM2". J. Biol. Chem. (United States) 278 (31): 29288–97.  
  31. ^ Lin, Ding-Yen; Shih Hsiu-Ming (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. (United States) 277 (28): 25446–56.  
  32. ^ Kamitani, T; Nguyen H P; Kito K; Fukuda-Kamitani T; Yeh E T (Feb 1998). "Covalent modification of PML by the sentrin family of ubiquitin-like proteins". J. Biol. Chem. (UNITED STATES) 273 (6): 3117–20.  

Further reading

  • Zhong S, Salomoni P, Pandolfi PP (2000). "The transcriptional role of PML and the nuclear body". Nat. Cell Biol. 2 (5): E85–90.  
  • Jensen K, Shiels C, Freemont PS (2001). "PML protein isoforms and the RBCC/TRIM motif". Oncogene 20 (49): 7223–33.  
  • Pearson M, Pelicci PG (2001). "PML interaction with p53 and its role in apoptosis and replicative senescence". Oncogene 20 (49): 7250–6.  
  • Salomoni P, Pandolfi PP (2002). "The role of PML in tumor suppression". Cell 108 (2): 165–70.  
  • Combes R, Balls M, Bansil L, et al. (2002). "An assessment of progress in the use of alternatives in toxicity testing since the publication of the report of the second FRAME Toxicity Committee (1991)". Alternatives to laboratory animals : ATLA 30 (4): 365–406.  
  • Bernardi R, Pandolfi PP (2004). "Role of PML and the PML-nuclear body in the control of programmed cell death". Oncogene 22 (56): 9048–57.  
  • Beez, S; Demmer, P; Puccetti, E (2012). "Targeting the Acute Promyelocytic Leukemia-Associated Fusion Proteins PML/RARα and PLZF/RARα with Interfering Peptides". PLOS ONE 7 (11): e48636.  

External links

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