Pml

Summary

Gene Symbol: Pml
Description: promyelocytic leukemia
Alias: RGD1562602, protein PML
Species: rat
Products:     Pml

Top Publications

  1. Bernardi R, Scaglioni P, Bergmann S, Horn H, Vousden K, Pandolfi P. PML regulates p53 stability by sequestering Mdm2 to the nucleolus. Nat Cell Biol. 2004;6:665-72 pubmed
    The promyelocytic leukaemia (PML) tumour-suppressor protein potentiates p53 function by regulating post-translational modifications, such as CBP-dependent acetylation and Chk2-dependent phosphorylation, in the PML-Nuclear Body (NB)...
  2. Condemine W, Takahashi Y, Zhu J, Puvion Dutilleul F, Guegan S, Janin A, et al. Characterization of endogenous human promyelocytic leukemia isoforms. Cancer Res. 2006;66:6192-8 pubmed
    Promyelocytic leukemia (PML) has been implicated in a variety of functions, including control of TP53 function and modulation of cellular senescence...
  3. Everett R, Rechter S, Papior P, Tavalai N, Stamminger T, Orr A. PML contributes to a cellular mechanism of repression of herpes simplex virus type 1 infection that is inactivated by ICP0. J Virol. 2006;80:7995-8005 pubmed
    Promyelocytic leukemia (PML) nuclear bodies (also known as ND10) are nuclear substructures that contain several proteins, including PML itself, Sp100, and hDaxx...
  4. de Stanchina E, Querido E, Narita M, Davuluri R, Pandolfi P, Ferbeyre G, et al. PML is a direct p53 target that modulates p53 effector functions. Mol Cell. 2004;13:523-35 pubmed
    ..Previous work suggests that the promyelocytic leukemia gene (PML) can act upstream of p53 to enhance transcription of p53 targets by recruiting p53 to nuclear bodies (NBs)...
  5. Kurki S, Latonen L, Laiho M. Cellular stress and DNA damage invoke temporally distinct Mdm2, p53 and PML complexes and damage-specific nuclear relocalization. J Cell Sci. 2003;116:3917-25 pubmed
    ..Here we demonstrate relocalization and novel interactions of Mdm2 with the promyelocytic leukemia (PML) protein following cellular stress and DNA damage...
  6. Xu Z, Timanova Atanasova A, Zhao R, Chang K. PML colocalizes with and stabilizes the DNA damage response protein TopBP1. Mol Cell Biol. 2003;23:4247-56 pubmed
    The PML tumor suppressor gene is consistently disrupted by t(15;17) in patients with acute promyelocytic leukemia...
  7. Wang Z, Ruggero D, Ronchetti S, Zhong S, Gaboli M, Rivi R, et al. PML is essential for multiple apoptotic pathways. Nat Genet. 1998;20:266-72 pubmed
    The PML gene of acute promyelocytic leukaemia (APL) encodes a cell growth and tumour suppressor, however, the mechanisms by which PML suppresses tumorigenesis are poorly understood...
  8. Tavalai N, Papior P, Rechter S, Leis M, Stamminger T. Evidence for a role of the cellular ND10 protein PML in mediating intrinsic immunity against human cytomegalovirus infections. J Virol. 2006;80:8006-18 pubmed
    ..of ND10, we generated primary human fibroblasts with a stable, short interfering RNA-mediated knockdown (kd) of PML. In these cells, other ND10-associated proteins like hDaxx showed a diffuse nuclear distribution...
  9. Wang Z, Delva L, Gaboli M, Rivi R, Giorgio M, Cordon Cardo C, et al. Role of PML in cell growth and the retinoic acid pathway. Science. 1998;279:1547-51 pubmed
    The PML gene is fused to the retinoic acid receptor alpha (RARalpha) gene in chromosomal translocations associated with acute promyelocytic leukemia (APL)...

More Information

Publications60

  1. Mu Z, Chin K, Liu J, Lozano G, Chang K. PML, a growth suppressor disrupted in acute promyelocytic leukemia. Mol Cell Biol. 1994;14:6858-67 pubmed
    ..The breakpoint site encodes fusion protein PML-RAR alpha, which is able to form a heterodimer with PML...
  2. Sternsdorf T, Jensen K, Züchner D, Will H. Cellular localization, expression, and structure of the nuclear dot protein 52. J Cell Biol. 1997;138:435-48 pubmed
    Nuclear dots containing PML and Sp100 proteins (NDs) play a role in the development of acute promyelocytic leukemia, are modified after infection with various viruses, and are autoimmunogenic in patients with primary biliary cirrhosis (..
  3. Lin H, Bergmann S, Pandolfi P. Cytoplasmic PML function in TGF-beta signalling. Nature. 2004;431:205-11 pubmed
    ..The promyelocytic leukaemia (PML) tumour suppressor of acute promyelocytic leukaemia (APL) accumulates in the PML nuclear body, but cytoplasmic PML ..
  4. Pearson M, Carbone R, Sebastiani C, Cioce M, Fagioli M, Saito S, et al. PML regulates p53 acetylation and premature senescence induced by oncogenic Ras. Nature. 2000;406:207-10 pubmed
    ..The mechanism of p53 activation by oncogenes remains largely unknown. Here we report that the tumour suppressor PML regulates the p53 response to oncogenic signals...
  5. Guo A, Salomoni P, Luo J, Shih A, Zhong S, Gu W, et al. The function of PML in p53-dependent apoptosis. Nat Cell Biol. 2000;2:730-6 pubmed
    The PML gene of acute promyelocytic leukaemia (APL) encodes a growth- and tumour-suppresor protein that is essential for several apoptotic signals. The mechanisms by which PML exerts its pro-apoptotic function are still unknown...
  6. Kawai T, Akira S, Reed J. ZIP kinase triggers apoptosis from nuclear PML oncogenic domains. Mol Cell Biol. 2003;23:6174-86 pubmed
    b>PML oncogenic domains (PODs), also referred to as nuclear dot 10 bodies, Kreb's bodies, or nuclear bodies, represent nuclear structures implicated in the regulation of a variety of cellular processes, including transcription, tumor ..
  7. Yang S, Kuo C, Bisi J, Kim M. PML-dependent apoptosis after DNA damage is regulated by the checkpoint kinase hCds1/Chk2. Nat Cell Biol. 2002;4:865-70 pubmed
    The promyelocytic leukaemia (PML) gene is translocated in most acute promyelocytic leukaemias and encodes a tumour suppressor protein...
  8. Takahashi K, Yoshida N, Murakami N, Kawata K, Ishizaki H, Tanaka Okamoto M, et al. Dynamic regulation of p53 subnuclear localization and senescence by MORC3. Mol Biol Cell. 2007;18:1701-9 pubmed
    ..The activity of p53 is regulated by recruitment into promyelocytic leukemia (PML)-nuclear bodies (NBs) as well as by stabilization through posttranslational modifications such as phosphorylation ..
  9. Fogal V, Gostissa M, Sandy P, Zacchi P, Sternsdorf T, Jensen K, et al. Regulation of p53 activity in nuclear bodies by a specific PML isoform. EMBO J. 2000;19:6185-95 pubmed
    Covalent modification of the promyelocytic leukaemia protein (PML) by SUMO-1 is a prerequisite for the assembly of nuclear bodies (NBs), subnuclear structures disrupted in various human diseases and linked to transcriptional and growth ..
  10. Zhong S, Muller S, Ronchetti S, Freemont P, Dejean A, Pandolfi P. Role of SUMO-1-modified PML in nuclear body formation. Blood. 2000;95:2748-52 pubmed
    The tumor-suppressive promyelocytic leukemia (PML) protein of acute promyelocytic leukemia (APL) has served as one of the defining components of a class of distinctive nuclear bodies (NBs)...
  11. Ulbricht T, Alzrigat M, Horch A, Reuter N, von Mikecz A, Steimle V, et al. PML promotes MHC class II gene expression by stabilizing the class II transactivator. J Cell Biol. 2012;199:49-63 pubmed publisher
    Promyelocytic leukemia (PML) nuclear bodies selectively associate with transcriptionally active genomic regions, including the gene-rich major histocompatibility (MHC) locus...
  12. Neault M, Mallette F, Vogel G, Michaud Levesque J, Richard S. Ablation of PRMT6 reveals a role as a negative transcriptional regulator of the p53 tumor suppressor. Nucleic Acids Res. 2012;40:9513-21 pubmed publisher
    ..PRMT6(-/-) MEFs displayed high transcriptional levels of p53 and its targets, p21 and PML. Generation of PRMT6(-/-); p53(-/-) MEFs prevented the premature senescence, suggesting that the induction of ..
  13. Zheng P, Guo Y, Niu Q, Levy D, Dyck J, Lu S, et al. Proto-oncogene PML controls genes devoted to MHC class I antigen presentation. Nature. 1998;396:373-6 pubmed
    ..Here we report that the proto-oncogene product PML induces expression of LMP-2, LMP-7, TAP-1 and TAP-2 in an MHC-class I-negative, recurrent tumour, leading to the re-..
  14. Tatematsu K, Yoshimoto N, Koyanagi T, Tokunaga C, Tachibana T, Yoneda Y, et al. Nuclear-cytoplasmic shuttling of a RING-IBR protein RBCK1 and its functional interaction with nuclear body proteins. J Biol Chem. 2005;280:22937-44 pubmed
    ..was found to interact with nuclear body proteins, CREB-binding protein (CBP), and promyelocytic leukemia protein (PML). Coexpression of RBCK1 with CBP significantly enhanced the transcriptional activity of RBCK1...
  15. Borden K, Boddy M, Lally J, O Reilly N, Martin S, Howe K, et al. The solution structure of the RING finger domain from the acute promyelocytic leukaemia proto-oncoprotein PML. EMBO J. 1995;14:1532-41 pubmed
    ..APL) has been ascribed to a chromosomal translocation event which results in a fusion protein comprising the PML protein and the retinoic acid receptor alpha...
  16. Liu J, Song Y, Qian J, Liu B, Dong Y, Tian B, et al. Promyelocytic leukemia protein interacts with werner syndrome helicase and regulates double-strand break repair in ?-irradiation-induced DNA damage responses. Biochemistry (Mosc). 2011;76:550-4 pubmed publisher
    ..The relocation of WRN after irradiation was perturbed by promyelocytic leukemia protein (PML) knockdown and enhanced by PML IV overexpression. PML IV physically interacted with WRN after irradiation...
  17. Marchesini M, Matocci R, Tasselli L, Cambiaghi V, Orleth A, Furia L, et al. PML is required for telomere stability in non-neoplastic human cells. Oncogene. 2016;35:1811-21 pubmed publisher
    ..Expression of the leukemia protein PML/RARα in hematopoietic progenitors displaces PML from telomeres and induces telomere shortening in the bone ..
  18. Wu W, Vallian S, Seto E, Yang W, Edmondson D, Roth S, et al. The growth suppressor PML represses transcription by functionally and physically interacting with histone deacetylases. Mol Cell Biol. 2001;21:2259-68 pubmed
    ..PML is associated with HDAC in vivo and directly interacts with HDAC in vitro. The fusion protein PML-RARalpha encoded by the t(15;17) breakpoint interacts with HDAC poorly...
  19. Koken M, Reid A, Quignon F, Chelbi Alix M, Davies J, Kabarowski J, et al. Leukemia-associated retinoic acid receptor alpha fusion partners, PML and PLZF, heterodimerize and colocalize to nuclear bodies. Proc Natl Acad Sci U S A. 1997;94:10255-60 pubmed
    ..promyelocytic leukemia (APL), the typical t(15;17) and the rare t(11;17) translocations express, respectively, the PML/RARalpha and PLZF/RARalpha fusion proteins (where RARalpha is retinoic acid receptor alpha)...
  20. Ishov A, Vladimirova O, Maul G. Heterochromatin and ND10 are cell-cycle regulated and phosphorylation-dependent alternate nuclear sites of the transcription repressor Daxx and SWI/SNF protein ATRX. J Cell Sci. 2004;117:3807-20 pubmed
    ..transcription repressor Daxx and the SWI/SNF protein ATRX are both associated with two intranuclear domains: ND10/PML bodies and heterochromatin...
  21. Salomoni P, Bernardi R, Bergmann S, Changou A, Tuttle S, Pandolfi P. The promyelocytic leukemia protein PML regulates c-Jun function in response to DNA damage. Blood. 2005;105:3686-90 pubmed
    The promyelocytic leukemia (PML) gene, a tumor suppressor inactivated in acute promyelocytic leukemia (APL), regulates apoptosis induced by DNA damage...
  22. Mu Z, Le X, Vallian S, Glassman A, Chang K. Stable overexpression of PML alters regulation of cell cycle progression in HeLa cells. Carcinogenesis. 1997;18:2063-9 pubmed
    Our previous studies demonstrated that PML is a growth suppressor that suppresses oncogenic transformation of NIH/3T3 cells and rat embryo fibroblasts...
  23. Satow R, Shitashige M, Jigami T, Fukami K, Honda K, Kitabayashi I, et al. ?-catenin inhibits promyelocytic leukemia protein tumor suppressor function in colorectal cancer cells. Gastroenterology. 2012;142:572-81 pubmed publisher
    Loss of promyelocytic leukemia protein (PML) nuclear body (NB) formation has been reported in colorectal and other solid tumors...
  24. Tao R, Berkova Z, Wise J, Rezaeian A, Daniluk U, Ao X, et al. PMLRAR? binds to Fas and suppresses Fas-mediated apoptosis through recruiting c-FLIP in vivo. Blood. 2011;118:3107-18 pubmed publisher
    ..We identified promyelocytic leukemia protein (PML) as a Fas-interacting protein using mass spectrometry analysis...
  25. Bernardi R, Guernah I, Jin D, Grisendi S, Alimonti A, Teruya Feldstein J, et al. PML inhibits HIF-1alpha translation and neoangiogenesis through repression of mTOR. Nature. 2006;442:779-85 pubmed
    Loss of the promyelocytic leukaemia (PML) tumour suppressor has been observed in several human cancers. The tumour-suppressive function of PML has been attributed to its ability to induce growth arrest, cellular senescence and apoptosis...
  26. Ecsedy J, Michaelson J, Leder P. Homeodomain-interacting protein kinase 1 modulates Daxx localization, phosphorylation, and transcriptional activity. Mol Cell Biol. 2003;23:950-60 pubmed
    ..Daxx normally resides within the nucleus in promyelocytic leukemia protein (PML) oncogenic domains (PODs), where it physically interacts with PML...
  27. Oh W, Ghim J, Lee E, Yang M, Kim E, Ahn J, et al. PML-IV functions as a negative regulator of telomerase by interacting with TERT. J Cell Sci. 2009;122:2613-22 pubmed publisher
    ..reverse transcriptase (TERT), a catalytic component of telomerase, is recruited to promyelocytic leukemia (PML) nuclear bodies through its interaction with PML-IV...
  28. Tang M, Liang Y, Chan J, Wong S, Chen E, Yao Y, et al. Promyelocytic leukemia (PML) protein plays important roles in regulating cell adhesion, morphology, proliferation and migration. PLoS ONE. 2013;8:e59477 pubmed publisher
    b>PML protein plays important roles in regulating cellular homeostasis. It forms PML nuclear bodies (PML-NBs) that act like nuclear relay stations and participate in many cellular functions...
  29. Wimmer P, Schreiner S, Everett R, Sirma H, Groitl P, Dobner T. SUMO modification of E1B-55K oncoprotein regulates isoform-specific binding to the tumour suppressor protein PML. Oncogene. 2010;29:5511-22 pubmed publisher
    ..that E1B-55K physically interacts with different isoforms of the tumour suppressor protein promyelocytic leukaemia (PML). We show that E1B-55K binds to PML isoforms IV and V in a SUMO1-dependent and -independent manner...
  30. Li W, Ferguson B, Khaled W, Tevendale M, Stingl J, Poli V, et al. PML depletion disrupts normal mammary gland development and skews the composition of the mammary luminal cell progenitor pool. Proc Natl Acad Sci U S A. 2009;106:4725-30 pubmed publisher
    Nuclear domains of promyelocytic leukemia protein (PML) are known to act as signaling nodes in many cellular processes...
  31. Evdokimov E, Sharma P, Lockett S, Lualdi M, Kuehn M. Loss of SUMO1 in mice affects RanGAP1 localization and formation of PML nuclear bodies, but is not lethal as it can be compensated by SUMO2 or SUMO3. J Cell Sci. 2008;121:4106-13 pubmed publisher
    ..Our study points to compensatory utilization of SUMO2 and/or SUMO3 for sumoylation of SUMO1 targets. The ability of SUMO isoforms to substitute for one another has important implications for rational targeting of the SUMO pathway. ..
  32. Qin Q, Inatome R, Hotta A, Kojima M, Yamamura H, Hirai H, et al. A novel GTPase, CRAG, mediates promyelocytic leukemia protein-associated nuclear body formation and degradation of expanded polyglutamine protein. J Cell Biol. 2006;172:497-504 pubmed
    ..irradiation, CRAG interacted with and induced an enlarged ring-like structure of promyelocytic leukemia protein (PML) body in a GTPase-dependent manner...
  33. Le X, Vallian S, Mu Z, Hung M, Chang K. Recombinant PML adenovirus suppresses growth and tumorigenicity of human breast cancer cells by inducing G1 cell cycle arrest and apoptosis. Oncogene. 1998;16:1839-49 pubmed
    Our previous studies demonstrated that the promyelocytic leukemia gene, PML which involved in the 15;17 translocation in acute promyelocytic leukemia (APL) is a growth and transformation suppressor...
  34. Langley E, Pearson M, Faretta M, Bauer U, Frye R, Minucci S, et al. Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence. EMBO J. 2002;21:2383-96 pubmed
    ..Here, we show that SIRT1, the human Sir2 homolog, is recruited to the promyelocytic leukemia protein (PML) nuclear bodies of mammalian cells upon overexpression of either PML or oncogenic Ras (Ha-rasV12)...
  35. Shen T, Lin H, Scaglioni P, Yung T, Pandolfi P. The mechanisms of PML-nuclear body formation. Mol Cell. 2006;24:331-9 pubmed
    b>PML nuclear bodies (NBs) are nuclear structures that have been implicated in processes such as transcriptional regulation, genome stability, response to viral infection, apoptosis, and tumor suppression...
  36. Giorgi C, Ito K, Lin H, Santangelo C, Wieckowski M, Lebiedzinska M, et al. PML regulates apoptosis at endoplasmic reticulum by modulating calcium release. Science. 2010;330:1247-51 pubmed publisher
    The promyelocytic leukemia (PML) tumor suppressor is a pleiotropic modulator of apoptosis. However, the molecular basis for such a diverse proapoptotic role is currently unknown...
  37. Sternsdorf T, Jensen K, Will H. Evidence for covalent modification of the nuclear dot-associated proteins PML and Sp100 by PIC1/SUMO-1. J Cell Biol. 1997;139:1621-34 pubmed
    b>PML and Sp100 proteins are associated with nuclear domains, known as nuclear dots (NDs). They were discovered in the context of leukemic transformation and as an autoantigen in primary biliary cirrhosis, respectively...
  38. Zhong S, Salomoni P, Ronchetti S, Guo A, Ruggero D, Pandolfi P. Promyelocytic leukemia protein (PML) and Daxx participate in a novel nuclear pathway for apoptosis. J Exp Med. 2000;191:631-40 pubmed
    The promyelocytic leukemia protein (PML) gene of acute promyelocytic leukemia (APL) encodes a cell growth and tumor suppressor essential for multiple apoptotic signals...
  39. Hsu J, Lin T, Tsai R. Nucleostemin prevents telomere damage by promoting PML-IV recruitment to SUMOylated TRF1. J Cell Biol. 2012;197:613-24 pubmed publisher
    ..of telomere (ALT) cells and decreased the percentage of damaged telomeres associated with ALT-associated PML bodies (APB) and the number of APB in ALT cells...
  40. Miki T, Xu Z, Chen Goodspeed M, Liu M, Van Oort Jansen A, Rea M, et al. PML regulates PER2 nuclear localization and circadian function. EMBO J. 2012;31:1427-39 pubmed publisher
    ..Here, we show that the tumour suppressor promyelocytic leukaemia (PML) protein is a circadian clock regulator and can physically interact with PER2...
  41. Duprez E, Saurin A, Desterro J, Lallemand Breitenbach V, Howe K, Boddy M, et al. SUMO-1 modification of the acute promyelocytic leukaemia protein PML: implications for nuclear localisation. J Cell Sci. 1999;112 ( Pt 3):381-93 pubmed
    ..We also find that the APL-associated fusion protein PML-RARA is efficiently modified in vitro, resulting in a specific and SUMO-1-dependent degradation of PML-RARA...
  42. Borden K, Lally J, Martin S, O Reilly N, Solomon E, Freemont P. In vivo and in vitro characterization of the B1 and B2 zinc-binding domains from the acute promyelocytic leukemia protooncoprotein PML. Proc Natl Acad Sci U S A. 1996;93:1601-6 pubmed
    ..APL) has been ascribed to a chromosomal translocation event which results in a fusion protein comprising the PML protein and retinoic acid receptor alpha...
  43. Yang Q, Liao L, Deng X, Chen R, Gray N, Yates J, et al. BMK1 is involved in the regulation of p53 through disrupting the PML-MDM2 interaction. Oncogene. 2013;32:3156-64 pubmed publisher
    Promyelocytic leukemia protein (PML) modulates the p53 tumor suppressor through its interaction with p53 and MDM2...
  44. Rabellino A, Carter B, Konstantinidou G, Wu S, Rimessi A, Byers L, et al. The SUMO E3-ligase PIAS1 regulates the tumor suppressor PML and its oncogenic counterpart PML-RARA. Cancer Res. 2012;72:2275-84 pubmed publisher
    ..In a broad spectrum of cancers, the tumor suppressor PML undergoes ubiquitin-mediated degradation primed by CK2 phosphorylation...
  45. Lin D, Huang Y, Jeng J, Kuo H, Chang C, Chao T, et al. Role of SUMO-interacting motif in Daxx SUMO modification, subnuclear localization, and repression of sumoylated transcription factors. Mol Cell. 2006;24:341-54 pubmed
    ..corepressor, was reported to repress the transcriptional potential of several transcription factors and target to PML oncogenic domains (PODs) via SUMO-dependent interactions...
  46. Shimada N, Shinagawa T, Ishii S. Modulation of M2-type pyruvate kinase activity by the cytoplasmic PML tumor suppressor protein. Genes Cells. 2008;13:245-54 pubmed publisher
    The promyelocytic leukemia (PML) tumor suppressor protein accumulates in PML nuclear bodies (PML-NBs), and can induce growth arrest, cellular senescence and apoptosis...
  47. Peche L, Scolz M, Ladelfa M, Monte M, Schneider C. MageA2 restrains cellular senescence by targeting the function of PMLIV/p53 axis at the PML-NBs. Cell Death Differ. 2012;19:926-36 pubmed publisher
    ..The promyelocytic leukemia (PML) tumor suppressor is a regulator of p53 acetylation and function in cellular senescence...
  48. Martin N, Benhamed M, Nacerddine K, Demarque M, Van Lohuizen M, Dejean A, et al. Physical and functional interaction between PML and TBX2 in the establishment of cellular senescence. EMBO J. 2012;31:95-109 pubmed publisher
    Cellular senescence acts as a potent barrier for tumour initiation and progression. Previous studies showed that the PML tumour suppressor promotes senescence, although the precise mechanisms remain to be elucidated...
  49. Rokudai S, Laptenko O, Arnal S, 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;110:3895-900 pubmed publisher
    ..here that MOZ is an acetyltransferase of p53 at K120 and K382 and colocalizes with p53 in promyelocytic leukemia (PML) nuclear bodies following cellular stress...
  50. Cho G, Lim Y, Golden J. SUMO interaction motifs in Sizn1 are required for promyelocytic leukemia protein nuclear body localization and for transcriptional activation. J Biol Chem. 2009;284:19592-600 pubmed publisher
    ..Here, we report that Sizn1 localizes to promyelocytic leukemia protein nuclear bodies (PML-NBs)...
  51. Alcalay M, Tomassoni L, Colombo E, Stoldt S, Grignani F, Fagioli M, et al. The promyelocytic leukemia gene product (PML) forms stable complexes with the retinoblastoma protein. Mol Cell Biol. 1998;18:1084-93 pubmed
    b>PML is a nuclear protein with growth-suppressive properties originally identified in the context of the PML-retinoic acid receptor alpha (RAR alpha) fusion protein of acute promyelocytic leukemia...