Protein PML

Details

Name
Protein PML
Synonyms
  • MYL
  • PP8675
  • Promyelocytic leukemia protein
  • RING finger protein 71
  • RNF71
  • TRIM19
  • Tripartite motif-containing protein 19
Gene Name
PML
Organism
Humans
Amino acid sequence
>lcl|BSEQ0009837|Protein PML
MEPAPARSPRPQQDPARPQEPTMPPPETPSEGRQPSPSPSPTERAPASEEEFQFLRCQQC
QAEAKCPKLLPCLHTLCSGCLEASGMQCPICQAPWPLGADTPALDNVFFESLQRRLSVYR
QIVDAQAVCTRCKESADFWCFECEQLLCAKCFEAHQWFLKHEARPLAELRNQSVREFLDG
TRKTNNIFCSNPNHRTPTLTSIYCRGCSKPLCCSCALLDSSHSELKCDISAEIQQRQEEL
DAMTQALQEQDSAFGAVHAQMHAAVGQLGRARAETEELIRERVRQVVAHVRAQERELLEA
VDARYQRDYEEMASRLGRLDAVLQRIRTGSALVQRMKCYASDQEVLDMHGFLRQALCRLR
QEEPQSLQAAVRTDGFDEFKVRLQDLSSCITQGKDAAVSKKASPEAASTPRDPIDVDLPE
EAERVKAQVQALGLAEAQPMAVVQSVPGAHPVPVYAFSIKGPSYGEDVSNTTTAQKRKCS
QTQCPRKVIKMESEEGKEARLARSSPEQPRPSTSKAVSPPHLDGPPSPRSPVIGSEVFLP
NSNHVASGAGEAEERVVVISSSEDSDAENSSSRELDDSSSESSDLQLEGPSTLRVLDENL
ADPQAEDRPLVFFDLKIDNETQKISQLAAVNRESKFRVVIQPEAFFSIYSKAVSLEVGLQ
HFLSFLSSMRRPILACYKLWGPGLPNFFRALEDINRLWEFQEAISGFLAALPLIRERVPG
ASSFKLKNLAQTYLARNMSERSAMAAVLAMRDLCRLLEVSPGPQLAQHVYPFSSLQCFAS
LQPLVQAAVLPRAEARLLALHNVSFMELLSAHRRDRQGGLKKYSRYLSLQTTTLPPAQPA
FNLQALGTYFEGLLEGPALARAEGVSTPLAGRGLAERASQQS
Number of residues
882
Molecular Weight
97549.475
Theoretical pI
Not Available
GO Classification
Functions
cobalt ion binding / DNA binding / protein heterodimerization activity / protein homodimerization activity / SMAD binding / SUMO binding / transcription coactivator activity / ubiquitin protein ligase binding / zinc ion binding
Processes
activation of cysteine-type endopeptidase activity involved in apoptotic process / apoptotic process / branching involved in mammary gland duct morphogenesis / cell cycle arrest / cell fate commitment / cellular response to interleukin-4 / cellular senescence / circadian regulation of gene expression / common-partner SMAD protein phosphorylation / defense response to virus / DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest / endoplasmic reticulum calcium ion homeostasis / entrainment of circadian clock by photoperiod / extrinsic apoptotic signaling pathway / fibroblast migration / innate immune response / interferon-gamma-mediated signaling pathway / intrinsic apoptotic signaling pathway in response to DNA damage / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / intrinsic apoptotic signaling pathway in response to oxidative stress / maintenance of protein location in nucleus / myeloid cell differentiation / negative regulation of angiogenesis / negative regulation of cell growth / negative regulation of cell proliferation / negative regulation of interleukin-1 beta secretion / negative regulation of mitotic cell cycle / negative regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process / negative regulation of telomerase activity / negative regulation of telomere maintenance via telomerase / negative regulation of transcription, DNA-templated / negative regulation of translation in response to oxidative stress / negative regulation of viral release from host cell / PML body organization / positive regulation of apoptotic process involved in mammary gland involution / positive regulation of defense response to virus by host / positive regulation of extrinsic apoptotic signaling pathway / positive regulation of fibroblast proliferation / positive regulation of histone deacetylation / positive regulation of MHC class I biosynthetic process / positive regulation of protein localization to chromosome, telomeric region / positive regulation of telomere maintenance / positive regulation of transcription from RNA polymerase II promoter / proteasome-mediated ubiquitin-dependent protein catabolic process / protein complex assembly / protein stabilization / protein targeting / regulation of calcium ion transport into cytosol / regulation of cell adhesion / regulation of circadian rhythm / regulation of double-strand break repair / regulation of protein phosphorylation / regulation of signal transduction by p53 class mediator / regulation of transcription, DNA-templated / response to cytokine / response to gamma radiation / response to hypoxia / response to UV / retinoic acid receptor signaling pathway / SMAD protein import into nucleus / transcription, DNA-templated / transforming growth factor beta receptor signaling pathway / viral process
Components
cytoplasm / cytosol / early endosome membrane / extrinsic component of endoplasmic reticulum membrane / heterochromatin / nuclear chromosome, telomeric region / nuclear matrix / nuclear membrane / nucleolus / nucleoplasm / nucleus / PML body
General Function
Functions via its association with PML-nuclear bodies (PML-NBs) in a wide range of important cellular processes, including tumor suppression, transcriptional regulation, apoptosis, senescence, DNA damage response, and viral defense mechanisms. Acts as the scaffold of PML-NBs allowing other proteins to shuttle in and out, a process which is regulated by SUMO-mediated modifications and interactions. Isoform PML-4 has a multifaceted role in the regulation of apoptosis and growth suppression: activates RB1 and inhibits AKT1 via interactions with PP1 and PP2A phosphatases respectively, negatively affects the PI3K pathway by inhibiting MTOR and activating PTEN, and positively regulates p53/TP53 by acting at different levels (by promoting its acetylation and phosphorylation and by inhibiting its MDM2-dependent degradation). Isoform PML-4 also: acts as a transcriptional repressor of TBX2 during cellular senescence and the repression is dependent on a functional RBL2/E2F4 repressor complex, regulates double-strand break repair in gamma-irradiation-induced DNA damage responses via its interaction with WRN, acts as a negative regulator of telomerase by interacting with TERT, and regulates PER2 nuclear localization and circadian function. Isoform PML-6 inhibits specifically the activity of the tetrameric form of PKM. The nuclear isoforms (isoform PML-1, isoform PML-2, isoform PML-3, isoform PML-4 and isoform PML-5) in concert with SATB1 are involved in local chromatin-loop remodeling and gene expression regulation at the MHC-I locus. Isoform PML-2 is required for efficient IFN-gamma induced MHC II gene transcription via regulation of CIITA. Cytoplasmic PML is involved in the regulation of the TGF-beta signaling pathway. PML also regulates transcription activity of ELF4 and can act as an important mediator for TNF-alpha- and IFN-alpha-mediated inhibition of endothelial cell network formation and migration.
Specific Function
Cobalt ion binding
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0051295|Protein PML (PML)
ATGGAGCCTGCACCCGCCCGATCTCCGAGGCCCCAGCAGGACCCCGCCCGGCCCCAGGAG
CCCACCATGCCTCCCCCCGAGACCCCCTCTGAAGGCCGCCAGCCCAGCCCCAGCCCCAGC
CCTACAGAGCGAGCCCCCGCTTCGGAGGAGGAGTTCCAGTTTCTGCGCTGCCAGCAATGC
CAGGCGGAAGCCAAGTGCCCGAAGCTGCTGCCTTGTCTGCACACGCTGTGCTCAGGATGC
CTGGAGGCGTCGGGCATGCAGTGCCCCATCTGCCAGGCGCCCTGGCCCCTAGGTGCAGAC
ACACCCGCCCTGGATAACGTCTTTTTCGAGAGTCTGCAGCGGCGCCTGTCGGTGTACCGG
CAGATTGTGGATGCGCAGGCTGTGTGCACCCGCTGCAAAGAGTCGGCCGACTTCTGGTGC
TTTGAGTGCGAGCAGCTCCTCTGCGCCAAGTGCTTCGAGGCACACCAGTGGTTCCTCAAG
CACGAGGCCCGGCCCCTAGCAGAGCTGCGCAACCAGTCGGTGCGTGAGTTCCTGGACGGC
ACCCGCAAGACCAACAACATCTTCTGCTCCAACCCCAACCACCGCACCCCTACGCTGACC
AGCATCTACTGCCGAGGATGTTCCAAGCCGCTGTGCTGCTCGTGCGCGCTCCTTGACAGC
AGCCACAGTGAGCTCAAGTGCGACATCAGCGCAGAGATCCAGCAGCGACAGGAGGAGCTG
GACGCCATGACGCAGGCGCTGCAGGAGCAGGATAGTGCCTTTGGCGCGGTTCACGCGCAG
ATGCACGCGGCCGTCGGCCAGCTGGGCCGCGCGCGTGCCGAGACCGAGGAGCTGATCCGC
GAGCGCGTGCGCCAGGTGGTAGCTCACGTGCGGGCTCAGGAGCGCGAGCTGCTGGAGGCT
GTGGACGCGCGGTACCAGCGCGACTACGAGGAGATGGCCAGTCGGCTGGGCCGCCTGGAT
GCTGTGCTGCAGCGCATCCGCACGGGCAGCGCGCTGGTGCAGAGGATGAAGTGCTACGCC
TCGGACCAGGAGGTGCTGGACATGCACGGTTTCCTGCGCCAGGCGCTCTGCCGCCTGCGC
CAGGAGGAGCCCCAGAGCCTGCAAGCTGCCGTGCGCACCGATGGCTTCGACGAGTTCAAG
GTGCGCCTGCAGGACCTCAGCTCTTGCATCACCCAGGGGAAAGATGCAGCTGTATCCAAG
AAAGCCAGCCCAGAGGCTGCCAGCACTCCCAGGGACCCTATTGACGTTGACCTGCCCGAG
GAGGCAGAGAGAGTGAAGGCCCAGGTTCAGGCCCTGGGGCTGGCTGAAGCCCAGCCTATG
GCTGTGGTACAGTCAGTGCCCGGGGCACACCCCGTGCCAGTGTACGCCTTCTCCATCAAA
GGCCCTTCCTATGGAGAGGATGTCTCCAATACAACGACAGCCCAGAAGAGGAAGTGCAGC
CAGACCCAGTGCCCCAGGAAGGTCATCAAGATGGAGTCTGAGGAGGGGAAGGAGGCAAGG
TTGGCTCGGAGCTCCCCGGAGCAGCCCAGGCCCAGCACCTCCAAGGCAGTCTCACCACCC
CACCTGGATGGACCGCCTAGCCCCAGGAGCCCCGTCATAGGAAGTGAGGTCTTCCTGCCC
AACAGCAACCACGTGGCCAGTGGCGCCGGGGAGGCAGAGGAACGCGTTGTGGTGATCAGC
AGCTCGGAAGACTCAGATGCCGAAAACTCGTCCTCCCGAGAGCTGGATGACAGCAGCAGT
GAGTCCAGTGACCTCCAGCTGGAAGGCCCCAGCACCCTCAGGGTCCTGGACGAGAACCTT
GCTGACCCCCAAGCAGAAGACAGACCTCTGGTTTTCTTTGACCTCAAGATTGACAATGAA
ACCCAGAAGATTAGCCAGCTGGCTGCGGTGAACCGGGAAAGCAAGTTCCGCGTGGTCATC
CAGCCTGAAGCCTTCTTCAGCATCTACTCCAAGGCCGTGTCCCTGGAGGTGGGGCTGCAG
CACTTCCTCAGCTTTCTGAGCTCCATGCGCCGCCCTATCTTGGCCTGCTACAAGCTGTGG
GGGCCTGGCCTCCCAAACTTCTTCCGGGCCCTGGAGGACATTAACAGGCTGTGGGAATTC
CAGGAGGCCATCTCGGGCTTCCTGGCTGCCCTGCCTCTCATCCGGGAGCGTGTGCCCGGG
GCCAGCAGCTTCAAACTCAAGAACCTGGCCCAGACCTACCTGGCGAGAAACATGAGCGAG
CGCAGCGCCATGGCTGCCGTGCTGGCCATGCGTGACCTGTGCCGCCTCCTCGAGGTCTCC
CCGGGCCCCCAGCTGGCCCAGCATGTCTACCCCTTCAGTAGCCTGCAGTGCTTTGCCTCC
CTGCAGCCCCTGGTGCAGGCAGCTGTGCTGCCCCGGGCTGAGGCCCGCCTCCTGGCCCTA
CACAACGTGAGCTTCATGGAGCTGCTGAGTGCACACCGCCGTGACCGGCAGGGGGGCCTG
AAGAAGTACAGCCGCTATCTAAGCCTGCAGACCACCACGTTGCCCCCTGCCCAGCCTGCT
TTCAACCTGCAGGCTCTGGGCACCTACTTTGAAGGCCTGTTGGAGGGTCCGGCGCTGGCA
CGGGCAGAAGGAGTCTCCACCCCACTTGCTGGCCGTGGCTTGGCAGAGAGGGCCTCCCAG
CAGAGCTGA
Chromosome Location
15
Locus
15q24.1
External Identifiers
ResourceLink
UniProtKB IDP29590
UniProtKB Entry NamePML_HUMAN
HGNC IDHGNC:9113
General References
  1. de The H, Lavau C, Marchio A, Chomienne C, Degos L, Dejean A: The PML-RAR alpha fusion mRNA generated by the t(15;17) translocation in acute promyelocytic leukemia encodes a functionally altered RAR. Cell. 1991 Aug 23;66(4):675-84. [Article]
  2. Goddard AD, Borrow J, Freemont PS, Solomon E: Characterization of a zinc finger gene disrupted by the t(15;17) in acute promyelocytic leukemia. Science. 1991 Nov 29;254(5036):1371-4. [Article]
  3. Kastner P, Perez A, Lutz Y, Rochette-Egly C, Gaub MP, Durand B, Lanotte M, Berger R, Chambon P: Structure, localization and transcriptional properties of two classes of retinoic acid receptor alpha fusion proteins in acute promyelocytic leukemia (APL): structural similarities with a new family of oncoproteins. EMBO J. 1992 Feb;11(2):629-42. [Article]
  4. Kakizuka A, Miller WH Jr, Umesono K, Warrell RP Jr, Frankel SR, Murty VV, Dmitrovsky E, Evans RM: Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RAR alpha with a novel putative transcription factor, PML. Cell. 1991 Aug 23;66(4):663-74. [Article]
  5. Reymond A, Meroni G, Fantozzi A, Merla G, Cairo S, Luzi L, Riganelli D, Zanaria E, Messali S, Cainarca S, Guffanti A, Minucci S, Pelicci PG, Ballabio A: The tripartite motif family identifies cell compartments. EMBO J. 2001 May 1;20(9):2140-51. [Article]
  6. Zody MC, Garber M, Sharpe T, Young SK, Rowen L, O'Neill K, Whittaker CA, Kamal M, Chang JL, Cuomo CA, Dewar K, FitzGerald MG, Kodira CD, Madan A, Qin S, Yang X, Abbasi N, Abouelleil A, Arachchi HM, Baradarani L, Birditt B, Bloom S, Bloom T, Borowsky ML, Burke J, Butler J, Cook A, DeArellano K, DeCaprio D, Dorris L 3rd, Dors M, Eichler EE, Engels R, Fahey J, Fleetwood P, Friedman C, Gearin G, Hall JL, Hensley G, Johnson E, Jones C, Kamat A, Kaur A, Locke DP, Madan A, Munson G, Jaffe DB, Lui A, Macdonald P, Mauceli E, Naylor JW, Nesbitt R, Nicol R, O'Leary SB, Ratcliffe A, Rounsley S, She X, Sneddon KM, Stewart S, Sougnez C, Stone SM, Topham K, Vincent D, Wang S, Zimmer AR, Birren BW, Hood L, Lander ES, Nusbaum C: Analysis of the DNA sequence and duplication history of human chromosome 15. Nature. 2006 Mar 30;440(7084):671-5. [Article]
  7. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  8. Tong JH, Dong S, Geng JP, Huang W, Wang ZY, Sun GL, Chen SJ, Chen Z, Larsen CJ, Berger R: Molecular rearrangements of the MYL gene in acute promyelocytic leukemia (APL, M3) define a breakpoint cluster region as well as some molecular variants. Oncogene. 1992 Feb;7(2):311-6. [Article]
  9. Fujita K, Oba R, Harada H, Mori H, Niikura H, Isoyama K, Omine M: Cytogenetics, FISH and RT-PCR analysis of acute promyelocytic leukemia: structure of the fusion point in a case lacking classic t(15;17) translocation. Leuk Lymphoma. 2003 Jan;44(1):111-5. [Article]
  10. Kamitani T, Kito K, Nguyen HP, Wada H, Fukuda-Kamitani T, Yeh ET: Identification of three major sentrinization sites in PML. J Biol Chem. 1998 Oct 9;273(41):26675-82. [Article]
  11. Cao T, Duprez E, Borden KL, Freemont PS, Etkin LD: Ret finger protein is a normal component of PML nuclear bodies and interacts directly with PML. J Cell Sci. 1998 May;111 ( Pt 10):1319-29. [Article]
  12. Borden KL, Campbell Dwyer EJ, Salvato MS: An arenavirus RING (zinc-binding) protein binds the oncoprotein promyelocyte leukemia protein (PML) and relocates PML nuclear bodies to the cytoplasm. J Virol. 1998 Jan;72(1):758-66. [Article]
  13. Zhong S, Delva L, Rachez C, Cenciarelli C, Gandini D, Zhang H, Kalantry S, Freedman LP, Pandolfi PP: A RA-dependent, tumour-growth suppressive transcription complex is the target of the PML-RARalpha and T18 oncoproteins. Nat Genet. 1999 Nov;23(3):287-95. [Article]
  14. Zhong S, Salomoni P, Ronchetti S, Guo A, Ruggero D, Pandolfi PP: Promyelocytic leukemia protein (PML) and Daxx participate in a novel nuclear pathway for apoptosis. J Exp Med. 2000 Feb 21;191(4):631-40. [Article]
  15. Li H, Leo C, Zhu J, Wu X, O'Neil J, Park EJ, Chen JD: Sequestration and inhibition of Daxx-mediated transcriptional repression by PML. Mol Cell Biol. 2000 Mar;20(5):1784-96. [Article]
  16. Guo A, Salomoni P, Luo J, Shih A, Zhong S, Gu W, Pandolfi PP: The function of PML in p53-dependent apoptosis. Nat Cell Biol. 2000 Oct;2(10):730-6. [Article]
  17. Regad T, Saib A, Lallemand-Breitenbach V, Pandolfi PP, de The H, Chelbi-Alix MK: PML mediates the interferon-induced antiviral state against a complex retrovirus via its association with the viral transactivator. EMBO J. 2001 Jul 2;20(13):3495-505. [Article]
  18. Jensen K, Shiels C, Freemont PS: PML protein isoforms and the RBCC/TRIM motif. Oncogene. 2001 Oct 29;20(49):7223-33. [Article]
  19. Langley E, Pearson M, Faretta M, Bauer UM, Frye RA, Minucci S, Pelicci PG, Kouzarides T: Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence. EMBO J. 2002 May 15;21(10):2383-96. [Article]
  20. Best JL, Ganiatsas S, Agarwal S, Changou A, Salomoni P, Shirihai O, Meluh PB, Pandolfi PP, Zon LI: SUMO-1 protease-1 regulates gene transcription through PML. Mol Cell. 2002 Oct;10(4):843-55. [Article]
  21. Yang S, Kuo C, Bisi JE, Kim MK: PML-dependent apoptosis after DNA damage is regulated by the checkpoint kinase hCds1/Chk2. Nat Cell Biol. 2002 Nov;4(11):865-70. [Article]
  22. Blondel D, Regad T, Poisson N, Pavie B, Harper F, Pandolfi PP, De The H, Chelbi-Alix MK: Rabies virus P and small P products interact directly with PML and reorganize PML nuclear bodies. Oncogene. 2002 Nov 14;21(52):7957-70. [Article]
  23. Louria-Hayon I, Grossman T, Sionov RV, Alsheich O, Pandolfi PP, Haupt Y: The promyelocytic leukemia protein protects p53 from Mdm2-mediated inhibition and degradation. J Biol Chem. 2003 Aug 29;278(35):33134-41. Epub 2003 Jun 16. [Article]
  24. Xu ZX, Timanova-Atanasova A, Zhao RX, Chang KS: PML colocalizes with and stabilizes the DNA damage response protein TopBP1. Mol Cell Biol. 2003 Jun;23(12):4247-56. [Article]
  25. Fanelli M, Fantozzi A, De Luca P, Caprodossi S, Matsuzawa S, Lazar MA, Pelicci PG, Minucci S: The coiled-coil domain is the structural determinant for mammalian homologues of Drosophila Sina-mediated degradation of promyelocytic leukemia protein and other tripartite motif proteins by the proteasome. J Biol Chem. 2004 Feb 13;279(7):5374-9. Epub 2003 Nov 25. [Article]
  26. Suico MA, Yoshida H, Seki Y, Uchikawa T, Lu Z, Shuto T, Matsuzaki K, Nakao M, Li JD, Kai H: Myeloid Elf-1-like factor, an ETS transcription factor, up-regulates lysozyme transcription in epithelial cells through interaction with promyelocytic leukemia protein. J Biol Chem. 2004 Apr 30;279(18):19091-8. Epub 2004 Feb 19. [Article]
  27. Kojic S, Medeot E, Guccione E, Krmac H, Zara I, Martinelli V, Valle G, Faulkner G: The Ankrd2 protein, a link between the sarcomere and the nucleus in skeletal muscle. J Mol Biol. 2004 May 28;339(2):313-25. [Article]
  28. Bernardi R, Scaglioni PP, Bergmann S, Horn HF, Vousden KH, Pandolfi PP: PML regulates p53 stability by sequestering Mdm2 to the nucleolus. Nat Cell Biol. 2004 Jul;6(7):665-72. Epub 2004 Jun 13. [Article]
  29. Daniels MJ, Marson A, Venkitaraman AR: PML bodies control the nuclear dynamics and function of the CHFR mitotic checkpoint protein. Nat Struct Mol Biol. 2004 Nov;11(11):1114-21. Epub 2004 Oct 3. [Article]
  30. Lin HK, Bergmann S, Pandolfi PP: Cytoplasmic PML function in TGF-beta signalling. Nature. 2004 Sep 9;431(7005):205-11. [Article]
  31. Kim YE, Kim DY, Lee JM, Kim ST, Han TH, Ahn JH: Requirement of the coiled-coil domain of PML-RARalpha oncoprotein for localization, sumoylation, and inhibition of monocyte differentiation. Biochem Biophys Res Commun. 2005 May 13;330(3):746-54. [Article]
  32. Condemine W, Takahashi Y, Zhu J, Puvion-Dutilleul F, Guegan S, Janin A, de The H: Characterization of endogenous human promyelocytic leukemia isoforms. Cancer Res. 2006 Jun 15;66(12):6192-8. [Article]
  33. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48. [Article]
  34. Dellaire G, Ching RW, Ahmed K, Jalali F, Tse KC, Bristow RG, Bazett-Jones DP: Promyelocytic leukemia nuclear bodies behave as DNA damage sensors whose response to DNA double-strand breaks is regulated by NBS1 and the kinases ATM, Chk2, and ATR. J Cell Biol. 2006 Oct 9;175(1):55-66. [Article]
  35. Pampin M, Simonin Y, Blondel B, Percherancier Y, Chelbi-Alix MK: Cross talk between PML and p53 during poliovirus infection: implications for antiviral defense. J Virol. 2006 Sep;80(17):8582-92. [Article]
  36. Shen TH, Lin HK, Scaglioni PP, Yung TM, Pandolfi PP: The mechanisms of PML-nuclear body formation. Mol Cell. 2006 Nov 3;24(3):331-9. [Article]
  37. Shimada N, Shinagawa T, Ishii S: Modulation of M2-type pyruvate kinase activity by the cytoplasmic PML tumor suppressor protein. Genes Cells. 2008 Mar;13(3):245-54. doi: 10.1111/j.1365-2443.2008.01165.x. [Article]
  38. Hayakawa F, Abe A, Kitabayashi I, Pandolfi PP, Naoe T: Acetylation of PML is involved in histone deacetylase inhibitor-mediated apoptosis. J Biol Chem. 2008 Sep 5;283(36):24420-5. doi: 10.1074/jbc.M802217200. Epub 2008 Jul 11. [Article]
  39. Tavalai N, Papior P, Rechter S, Stamminger T: Nuclear domain 10 components promyelocytic leukemia protein and hDaxx independently contribute to an intrinsic antiviral defense against human cytomegalovirus infection. J Virol. 2008 Jan;82(1):126-37. Epub 2007 Oct 17. [Article]
  40. Song MS, Salmena L, Carracedo A, Egia A, Lo-Coco F, Teruya-Feldstein J, Pandolfi PP: The deubiquitinylation and localization of PTEN are regulated by a HAUSP-PML network. Nature. 2008 Oct 9;455(7214):813-7. doi: 10.1038/nature07290. Epub 2008 Aug 20. [Article]
  41. Tatham MH, Geoffroy MC, Shen L, Plechanovova A, Hattersley N, Jaffray EG, Palvimo JJ, Hay RT: RNF4 is a poly-SUMO-specific E3 ubiquitin ligase required for arsenic-induced PML degradation. Nat Cell Biol. 2008 May;10(5):538-46. doi: 10.1038/ncb1716. Epub 2008 Apr 13. [Article]
  42. Kumar PP, Bischof O, Purbey PK, Notani D, Urlaub H, Dejean A, Galande S: Functional interaction between PML and SATB1 regulates chromatin-loop architecture and transcription of the MHC class I locus. Nat Cell Biol. 2007 Jan;9(1):45-56. Epub 2006 Dec 17. [Article]
  43. McNally BA, Trgovcich J, Maul GG, Liu Y, Zheng P: A role for cytoplasmic PML in cellular resistance to viral infection. PLoS One. 2008 May 28;3(5):e2277. doi: 10.1371/journal.pone.0002277. [Article]
  44. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [Article]
  45. Li W, Wang G, Zhang H, Zhang D, Zeng J, Chen X, Xu Y, Li K: Differential suppressive effect of promyelocytic leukemia protein on the replication of different subtypes/strains of influenza A virus. Biochem Biophys Res Commun. 2009 Nov 6;389(1):84-9. doi: 10.1016/j.bbrc.2009.08.091. Epub 2009 Aug 22. [Article]
  46. Oh W, Ghim J, Lee EW, Yang MR, Kim ET, Ahn JH, Song J: PML-IV functions as a negative regulator of telomerase by interacting with TERT. J Cell Sci. 2009 Aug 1;122(Pt 15):2613-22. doi: 10.1242/jcs.048066. Epub 2009 Jun 30. [Article]
  47. Gresko E, Ritterhoff S, Sevilla-Perez J, Roscic A, Frobius K, Kotevic I, Vichalkovski A, Hess D, Hemmings BA, Schmitz ML: PML tumor suppressor is regulated by HIPK2-mediated phosphorylation in response to DNA damage. Oncogene. 2009 Feb 5;28(5):698-708. doi: 10.1038/onc.2008.420. Epub 2008 Nov 17. [Article]
  48. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [Article]
  49. Mimura Y, Takahashi K, Kawata K, Akazawa T, Inoue N: Two-step colocalization of MORC3 with PML nuclear bodies. J Cell Sci. 2010 Jun 15;123(Pt 12):2014-24. doi: 10.1242/jcs.063586. Epub 2010 May 25. [Article]
  50. Blondel D, Kheddache S, Lahaye X, Dianoux L, Chelbi-Alix MK: Resistance to rabies virus infection conferred by the PMLIV isoform. J Virol. 2010 Oct;84(20):10719-26. doi: 10.1128/JVI.01286-10. Epub 2010 Aug 11. [Article]
  51. Wimmer P, Schreiner S, Everett RD, Sirma H, Groitl P, Dobner T: SUMO modification of E1B-55K oncoprotein regulates isoform-specific binding to the tumour suppressor protein PML. Oncogene. 2010 Oct 7;29(40):5511-22. doi: 10.1038/onc.2010.284. Epub 2010 Jul 19. [Article]
  52. Geoffroy MC, Jaffray EG, Walker KJ, Hay RT: Arsenic-induced SUMO-dependent recruitment of RNF4 into PML nuclear bodies. Mol Biol Cell. 2010 Dec;21(23):4227-39. doi: 10.1091/mbc.E10-05-0449. Epub 2010 Oct 13. [Article]
  53. Hung MS, Lin YC, Mao JH, Kim IJ, Xu Z, Yang CT, Jablons DM, You L: Functional polymorphism of the CK2alpha intronless gene plays oncogenic roles in lung cancer. PLoS One. 2010 Jul 2;5(7):e11418. doi: 10.1371/journal.pone.0011418. [Article]
  54. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. [Article]
  55. Zhang XW, Yan XJ, Zhou ZR, Yang FF, Wu ZY, Sun HB, Liang WX, Song AX, Lallemand-Breitenbach V, Jeanne M, Zhang QY, Yang HY, Huang QH, Zhou GB, Tong JH, Zhang Y, Wu JH, Hu HY, de The H, Chen SJ, Chen Z: Arsenic trioxide controls the fate of the PML-RARalpha oncoprotein by directly binding PML. Science. 2010 Apr 9;328(5975):240-3. doi: 10.1126/science.1183424. [Article]
  56. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
  57. Liu J, Song Y, Qian J, Liu B, Dong Y, Tian B, Sun Z: Promyelocytic leukemia protein interacts with werner syndrome helicase and regulates double-strand break repair in gamma-irradiation-induced DNA damage responses. Biochemistry (Mosc). 2011 May;76(5):550-4. doi: 10.1134/S000629791105004X. [Article]
  58. Yuan WC, Lee YR, Huang SF, Lin YM, Chen TY, Chung HC, Tsai CH, Chen HY, Chiang CT, Lai CK, Lu LT, Chen CH, Gu DL, Pu YS, Jou YS, Lu KP, Hsiao PW, Shih HM, Chen RH: A Cullin3-KLHL20 Ubiquitin ligase-dependent pathway targets PML to potentiate HIF-1 signaling and prostate cancer progression. Cancer Cell. 2011 Aug 16;20(2):214-28. doi: 10.1016/j.ccr.2011.07.008. [Article]
  59. Pinton P, Giorgi C, Pandolfi PP: The role of PML in the control of apoptotic cell fate: a new key player at ER-mitochondria sites. Cell Death Differ. 2011 Sep;18(9):1450-6. doi: 10.1038/cdd.2011.31. Epub 2011 Apr 8. [Article]
  60. Carracedo A, Ito K, Pandolfi PP: The nuclear bodies inside out: PML conquers the cytoplasm. Curr Opin Cell Biol. 2011 Jun;23(3):360-6. doi: 10.1016/j.ceb.2011.03.011. Epub 2011 Apr 16. [Article]
  61. Lim JH, Liu Y, Reineke E, Kao HY: Mitogen-activated protein kinase extracellular signal-regulated kinase 2 phosphorylates and promotes Pin1 protein-dependent promyelocytic leukemia protein turnover. J Biol Chem. 2011 Dec 30;286(52):44403-11. doi: 10.1074/jbc.M111.289512. Epub 2011 Oct 27. [Article]
  62. Cuchet D, Sykes A, Nicolas A, Orr A, Murray J, Sirma H, Heeren J, Bartelt A, Everett RD: PML isoforms I and II participate in PML-dependent restriction of HSV-1 replication. J Cell Sci. 2011 Jan 15;124(Pt 2):280-91. doi: 10.1242/jcs.075390. Epub 2010 Dec 20. [Article]
  63. Geoffroy MC, Chelbi-Alix MK: Role of promyelocytic leukemia protein in host antiviral defense. J Interferon Cytokine Res. 2011 Jan;31(1):145-58. doi: 10.1089/jir.2010.0111. Epub 2011 Jan 3. [Article]
  64. Maroui MA, Pampin M, Chelbi-Alix MK: Promyelocytic leukemia isoform IV confers resistance to encephalomyocarditis virus via the sequestration of 3D polymerase in nuclear bodies. J Virol. 2011 Dec;85(24):13164-73. doi: 10.1128/JVI.05808-11. Epub 2011 Oct 12. [Article]
  65. Hattersley N, Shen L, Jaffray EG, Hay RT: The SUMO protease SENP6 is a direct regulator of PML nuclear bodies. Mol Biol Cell. 2011 Jan 1;22(1):78-90. doi: 10.1091/mbc.E10-06-0504. Epub 2010 Dec 9. [Article]
  66. Salomoni P, Betts-Henderson J: The role of PML in the nervous system. Mol Neurobiol. 2011 Apr;43(2):114-23. doi: 10.1007/s12035-010-8156-y. Epub 2010 Dec 15. [Article]
  67. Reichelt M, Wang L, Sommer M, Perrino J, Nour AM, Sen N, Baiker A, Zerboni L, Arvin AM: Entrapment of viral capsids in nuclear PML cages is an intrinsic antiviral host defense against varicella-zoster virus. PLoS Pathog. 2011 Feb 3;7(2):e1001266. doi: 10.1371/journal.ppat.1001266. [Article]
  68. Rigbolt KT, Prokhorova TA, Akimov V, Henningsen J, Johansen PT, Kratchmarova I, Kassem M, Mann M, Olsen JV, Blagoev B: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal. 2011 Mar 15;4(164):rs3. doi: 10.1126/scisignal.2001570. [Article]
  69. Rabellino A, Carter B, Konstantinidou G, Wu SY, Rimessi A, Byers LA, Heymach JV, Girard L, Chiang CM, Teruya-Feldstein J, Scaglioni PP: The SUMO E3-ligase PIAS1 regulates the tumor suppressor PML and its oncogenic counterpart PML-RARA. Cancer Res. 2012 May 1;72(9):2275-84. doi: 10.1158/0008-5472.CAN-11-3159. Epub 2012 Mar 9. [Article]
  70. Peche LY, Scolz M, Ladelfa MF, Monte M, Schneider C: MageA2 restrains cellular senescence by targeting the function of PMLIV/p53 axis at the PML-NBs. Cell Death Differ. 2012 Jun;19(6):926-36. doi: 10.1038/cdd.2011.173. Epub 2011 Nov 25. [Article]
  71. Salomoni P, Dvorkina M, Michod D: Role of the promyelocytic leukaemia protein in cell death regulation. Cell Death Dis. 2012 Jan 12;3:e247. doi: 10.1038/cddis.2011.122. [Article]
  72. Martin N, Benhamed M, Nacerddine K, Demarque MD, van Lohuizen M, Dejean A, Bischof O: Physical and functional interaction between PML and TBX2 in the establishment of cellular senescence. EMBO J. 2012 Jan 4;31(1):95-109. doi: 10.1038/emboj.2011.370. Epub 2011 Oct 14. [Article]
  73. Miki T, Xu Z, Chen-Goodspeed M, Liu M, Van Oort-Jansen A, Rea MA, Zhao Z, Lee CC, Chang KS: PML regulates PER2 nuclear localization and circadian function. EMBO J. 2012 Mar 21;31(6):1427-39. doi: 10.1038/emboj.2012.1. Epub 2012 Jan 24. [Article]
  74. Cheng X, Kao HY: Post-translational modifications of PML: consequences and implications. Front Oncol. 2013 Jan 4;2:210. doi: 10.3389/fonc.2012.00210. eCollection 2012. [Article]
  75. Satow R, Shitashige M, Jigami T, Fukami K, Honda K, Kitabayashi I, Yamada T: beta-catenin inhibits promyelocytic leukemia protein tumor suppressor function in colorectal cancer cells. Gastroenterology. 2012 Mar;142(3):572-81. doi: 10.1053/j.gastro.2011.11.041. Epub 2011 Dec 9. [Article]
  76. Okino Y, Inayoshi Y, Kojima Y, Kidani S, Kaneoka H, Honkawa A, Higuchi H, Nishijima K, Miyake K, Iijima S: Moloney murine leukemia virus integrase and reverse transcriptase interact with PML proteins. J Biochem. 2012 Aug;152(2):161-9. doi: 10.1093/jb/mvs063. Epub 2012 Jun 7. [Article]
  77. Cheng X, Liu Y, Chu H, Kao HY: Promyelocytic leukemia protein (PML) regulates endothelial cell network formation and migration in response to tumor necrosis factor alpha (TNFalpha) and interferon alpha (IFNalpha). J Biol Chem. 2012 Jul 6;287(28):23356-67. doi: 10.1074/jbc.M112.340505. Epub 2012 May 15. [Article]
  78. Geng Y, Monajembashi S, Shao A, Cui D, He W, Chen Z, Hemmerich P, Tang J: Contribution of the C-terminal regions of promyelocytic leukemia protein (PML) isoforms II and V to PML nuclear body formation. J Biol Chem. 2012 Aug 31;287(36):30729-42. doi: 10.1074/jbc.M112.374769. Epub 2012 Jul 7. [Article]
  79. Chen RH, Lee YR, Yuan WC: The role of PML ubiquitination in human malignancies. J Biomed Sci. 2012 Aug 30;19:81. doi: 10.1186/1423-0127-19-81. [Article]
  80. Ulbricht T, Alzrigat M, Horch A, Reuter N, von Mikecz A, Steimle V, Schmitt E, Kramer OH, Stamminger T, Hemmerich P: PML promotes MHC class II gene expression by stabilizing the class II transactivator. J Cell Biol. 2012 Oct 1;199(1):49-63. doi: 10.1083/jcb.201112015. Epub 2012 Sep 24. [Article]
  81. Carracedo A, Weiss D, Leliaert AK, Bhasin M, de Boer VC, Laurent G, Adams AC, Sundvall M, Song SJ, Ito K, Finley LS, Egia A, Libermann T, Gerhart-Hines Z, Puigserver P, Haigis MC, Maratos-Flier E, Richardson AL, Schafer ZT, Pandolfi PP: A metabolic prosurvival role for PML in breast cancer. J Clin Invest. 2012 Sep;122(9):3088-100. doi: 10.1172/JCI62129. Epub 2012 Aug 13. [Article]
  82. Cuchet-Lourenco D, Vanni E, Glass M, Orr A, Everett RD: Herpes simplex virus 1 ubiquitin ligase ICP0 interacts with PML isoform I and induces its SUMO-independent degradation. J Virol. 2012 Oct;86(20):11209-22. Epub 2012 Aug 8. [Article]
  83. Zhou H, Di Palma S, Preisinger C, Peng M, Polat AN, Heck AJ, Mohammed S: Toward a comprehensive characterization of a human cancer cell phosphoproteome. J Proteome Res. 2013 Jan 4;12(1):260-71. doi: 10.1021/pr300630k. Epub 2012 Dec 18. [Article]
  84. Yang Q, Liao L, Deng X, Chen R, Gray NS, Yates JR 3rd, Lee JD: BMK1 is involved in the regulation of p53 through disrupting the PML-MDM2 interaction. Oncogene. 2013 Jun 27;32(26):3156-64. doi: 10.1038/onc.2012.332. Epub 2012 Aug 6. [Article]
  85. Guan D, Factor D, Liu Y, Wang Z, Kao HY: The epigenetic regulator UHRF1 promotes ubiquitination-mediated degradation of the tumor-suppressor protein promyelocytic leukemia protein. Oncogene. 2013 Aug 15;32(33):3819-28. doi: 10.1038/onc.2012.406. Epub 2012 Sep 3. [Article]
  86. Maroui MA, Kheddache-Atmane S, El Asmi F, Dianoux L, Aubry M, Chelbi-Alix MK: Requirement of PML SUMO interacting motif for RNF4- or arsenic trioxide-induced degradation of nuclear PML isoforms. PLoS One. 2012;7(9):e44949. doi: 10.1371/journal.pone.0044949. Epub 2012 Sep 18. [Article]
  87. Kuroki M, Ariumi Y, Hijikata M, Ikeda M, Dansako H, Wakita T, Shimotohno K, Kato N: PML tumor suppressor protein is required for HCV production. Biochem Biophys Res Commun. 2013 Jan 11;430(2):592-7. doi: 10.1016/j.bbrc.2012.11.108. Epub 2012 Dec 5. [Article]
  88. Lo YH, Huang YW, Wu YH, Tsai CS, Lin YC, Mo ST, Kuo WC, Chuang YT, Jiang ST, Shih HM, Lai MZ: Selective inhibition of the NLRP3 inflammasome by targeting to promyelocytic leukemia protein in mouse and human. Blood. 2013 Apr 18;121(16):3185-94. doi: 10.1182/blood-2012-05-432104. Epub 2013 Feb 21. [Article]
  89. Berscheminski J, Groitl P, Dobner T, Wimmer P, Schreiner S: The adenoviral oncogene E1A-13S interacts with a specific isoform of the tumor suppressor PML to enhance viral transcription. J Virol. 2013 Jan;87(2):965-77. doi: 10.1128/JVI.02023-12. Epub 2012 Nov 7. [Article]
  90. Rokudai S, Laptenko O, Arnal SM, Taya Y, Kitabayashi I, Prives C: MOZ increases p53 acetylation and premature senescence through its complex formation with PML. Proc Natl Acad Sci U S A. 2013 Mar 5;110(10):3895-900. doi: 10.1073/pnas.1300490110. Epub 2013 Feb 19. [Article]
  91. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
  92. Hendriks IA, D'Souza RC, Yang B, Verlaan-de Vries M, Mann M, Vertegaal AC: Uncovering global SUMOylation signaling networks in a site-specific manner. Nat Struct Mol Biol. 2014 Oct;21(10):927-36. doi: 10.1038/nsmb.2890. Epub 2014 Sep 14. [Article]
  93. Hendriks IA, Treffers LW, Verlaan-de Vries M, Olsen JV, Vertegaal AC: SUMO-2 Orchestrates Chromatin Modifiers in Response to DNA Damage. Cell Rep. 2015 Mar 10. pii: S2211-1247(15)00179-5. doi: 10.1016/j.celrep.2015.02.033. [Article]
  94. Xiao Z, Chang JG, Hendriks IA, Sigurethsson JO, Olsen JV, Vertegaal AC: System-wide Analysis of SUMOylation Dynamics in Response to Replication Stress Reveals Novel Small Ubiquitin-like Modified Target Proteins and Acceptor Lysines Relevant for Genome Stability. Mol Cell Proteomics. 2015 May;14(5):1419-34. doi: 10.1074/mcp.O114.044792. Epub 2015 Mar 9. [Article]
  95. Wimmer P, Berscheminski J, Blanchette P, Groitl P, Branton PE, Hay RT, Dobner T, Schreiner S: PML isoforms IV and V contribute to adenovirus-mediated oncogenic transformation by functionally inhibiting the tumor-suppressor p53. Oncogene. 2016 Jan 7;35(1):69-82. doi: 10.1038/onc.2015.63. Epub 2015 Mar 16. [Article]
  96. Borden KL, Boddy MN, Lally J, O'Reilly NJ, Martin S, Howe K, Solomon E, Freemont PS: The solution structure of the RING finger domain from the acute promyelocytic leukaemia proto-oncoprotein PML. EMBO J. 1995 Apr 3;14(7):1532-41. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01169Arsenic trioxideapproved, investigationalunknownDetails