Promyelocytic Leukemia Protein (PML)

MYL; RNF71; TRIM19; Probable Transcription Factor PML; Ring Finger Protein 71; Tripartite motif-containing protein 19

SPN	U623
HGNC	9113
MGI	104662
PubMed	10684855
RGD	1562602
UniProt	P29590
Wiki	PML

Probable transcription factor PML 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.

Reference

"The PML-RAR alpha fusion mRNA generated by the t(15;17) translocation in acute promyelocytic leukemia encodes a functionally altered RAR."
Cell 66:675-684(1991) [PubMed] [Europe PMC] [Abstract]

"Characterization of a zinc finger gene disrupted by the t(15;17) in acute promyelocytic leukemia."
Science 254:1371-1374(1991) [PubMed] [Europe PMC] [Abstract]

"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. 11:629-642(1992) [PubMed] [Europe PMC] [Abstract]

"Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RAR alpha with a novel putative transcription factor, PML."
Cell 66:663-674(1991) [PubMed] [Europe PMC] [Abstract]

"The tripartite motif family identifies cell compartments."
EMBO J. 20:2140-2151(2001) [PubMed] [Europe PMC] [Abstract]

"Analysis of the DNA sequence and duplication history of human chromosome 15."
Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"Molecular rearrangements of the MYL gene in acute promyelocytic leukemia (APL, M3) define a breakpoint cluster region as well as some molecular variants."
Oncogene 7:311-316(1992) [PubMed] [Europe PMC] [Abstract]

"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 44:111-115(2003) [PubMed] [Europe PMC] [Abstract]

"Identification of three major sentrinization sites in PML."
J. Biol. Chem. 273:26675-26682(1998) [PubMed] [Europe PMC] [Abstract]

"Ret finger protein is a normal component of PML nuclear bodies and interacts directly with PML."
J. Cell Sci. 111:1319-1329(1998) [PubMed] [Europe PMC] [Abstract]

"An arenavirus RING (zinc-binding) protein binds the oncoprotein promyelocyte leukemia protein (PML) and relocates PML nuclear bodies to the cytoplasm."
J. Virol. 72:758-766(1998) [PubMed] [Europe PMC] [Abstract]

"A RA-dependent, tumour-growth suppressive transcription complex is the target of the PML-RARalpha and T18 oncoproteins."
Nat. Genet. 23:287-295(1999) [PubMed] [Europe PMC] [Abstract]

"Promyelocytic leukemia protein (PML) and Daxx participate in a novel nuclear pathway for apoptosis."
J. Exp. Med. 191:631-640(2000) [PubMed] [Europe PMC] [Abstract]

"Sequestration and inhibition of Daxx-mediated transcriptional repression by PML."
Mol. Cell. Biol. 20:1784-1796(2000) [PubMed] [Europe PMC] [Abstract]

"The function of PML in p53-dependent apoptosis."
Nat. Cell Biol. 2:730-736(2000) [PubMed] [Europe PMC] [Abstract]

"PML mediates the interferon-induced antiviral state against a complex retrovirus via its association with the viral transactivator."
EMBO J. 20:3495-3505(2001) [PubMed] [Europe PMC] [Abstract]

"PML protein isoforms and the RBCC/TRIM motif."
Oncogene 20:7223-7233(2001) [PubMed] [Europe PMC] [Abstract]

"Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence."
EMBO J. 21:2383-2396(2002) [PubMed] [Europe PMC] [Abstract]

"SUMO-1 protease-1 regulates gene transcription through PML."
Mol. Cell 10:843-855(2002) [PubMed] [Europe PMC] [Abstract]

"PML-dependent apoptosis after DNA damage is regulated by the checkpoint kinase hCds1/Chk2."
Nat. Cell Biol. 4:865-870(2002) [PubMed] [Europe PMC] [Abstract]

"Rabies virus P and small P products interact directly with PML and reorganize PML nuclear bodies."
Oncogene 21:7957-7970(2002) [PubMed] [Europe PMC] [Abstract]

"The promyelocytic leukemia protein protects p53 from Mdm2-mediated inhibition and degradation."
J. Biol. Chem. 278:33134-33141(2003) [PubMed] [Europe PMC] [Abstract]

"PML colocalizes with and stabilizes the DNA damage response protein TopBP1."
Mol. Cell. Biol. 23:4247-4256(2003) [PubMed] [Europe PMC] [Abstract]

"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. 279:5374-5379(2004) [PubMed] [Europe PMC] [Abstract]

"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. 279:19091-19098(2004) [PubMed] [Europe PMC] [Abstract]

"The Ankrd2 protein, a link between the sarcomere and the nucleus in skeletal muscle."
J. Mol. Biol. 339:313-325(2004) [PubMed] [Europe PMC] [Abstract]

"PML regulates p53 stability by sequestering Mdm2 to the nucleolus."
Nat. Cell Biol. 6:665-672(2004) [PubMed] [Europe PMC] [Abstract]

"PML bodies control the nuclear dynamics and function of the CHFR mitotic checkpoint protein."
Nat. Struct. Mol. Biol. 11:1114-1121(2004) [PubMed] [Europe PMC] [Abstract]

"Cytoplasmic PML function in TGF-beta signalling."
Nature 431:205-211(2004) [PubMed] [Europe PMC] [Abstract]

"Requirement of the coiled-coil domain of PML-RARalpha oncoprotein for localization, sumoylation, and inhibition of monocyte differentiation."
Biochem. Biophys. Res. Commun. 330:746-754(2005) [PubMed] [Europe PMC] [Abstract]

"Characterization of endogenous human promyelocytic leukemia isoforms."
Cancer Res. 66:6192-6198(2006) [PubMed] [Europe PMC] [Abstract]

"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]

"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. 175:55-66(2006) [PubMed] [Europe PMC] [Abstract]

"Cross talk between PML and p53 during poliovirus infection: implications for antiviral defense."
J. Virol. 80:8582-8592(2006) [PubMed] [Europe PMC] [Abstract]

"The mechanisms of PML-nuclear body formation."
Mol. Cell 24:331-339(2006) [PubMed] [Europe PMC] [Abstract]

"Modulation of M2-type pyruvate kinase activity by the cytoplasmic PML tumor suppressor protein."
Genes Cells 13:245-254(2008) [PubMed] [Europe PMC] [Abstract]

"Acetylation of PML is involved in histone deacetylase inhibitor-mediated apoptosis."
J. Biol. Chem. 283:24420-24425(2008) [PubMed] [Europe PMC] [Abstract]

"Nuclear domain 10 components promyelocytic leukemia protein and hDaxx independently contribute to an intrinsic antiviral defense against human cytomegalovirus infection."
J. Virol. 82:126-137(2008) [PubMed] [Europe PMC] [Abstract]

"The deubiquitinylation and localization of PTEN are regulated by a HAUSP-PML network."
Nature 455:813-817(2008) [PubMed] [Europe PMC] [Abstract]

"RNF4 is a poly-SUMO-specific E3 ubiquitin ligase required for arsenic-induced PML degradation."
Nat. Cell Biol. 10:538-546(2008) [PubMed] [Europe PMC] [Abstract]

"Functional interaction between PML and SATB1 regulates chromatin-loop architecture and transcription of the MHC class I locus."
Nat. Cell Biol. 9:45-56(2007) [PubMed] [Europe PMC] [Abstract]

"A role for cytoplasmic PML in cellular resistance to viral infection."
PLoS ONE 3:E2277-E2277(2008) [PubMed] [Europe PMC] [Abstract]

"A quantitative atlas of mitotic phosphorylation."
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]

"Differential suppressive effect of promyelocytic leukemia protein on the replication of different subtypes/strains of influenza A virus."
Biochem. Biophys. Res. Commun. 389:84-89(2009) [PubMed] [Europe PMC] [Abstract]

"PML-IV functions as a negative regulator of telomerase by interacting with TERT."
J. Cell Sci. 122:2613-2622(2009) [PubMed] [Europe PMC] [Abstract]

"PML tumor suppressor is regulated by HIPK2-mediated phosphorylation in response to DNA damage."
Oncogene 28:698-708(2009) [PubMed] [Europe PMC] [Abstract]

"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]

"Resistance to rabies virus infection conferred by the PMLIV isoform."
J. Virol. 84:10719-10726(2010) [PubMed] [Europe PMC] [Abstract]

"Arsenic-induced SUMO-dependent recruitment of RNF4 into PML nuclear bodies."
Mol. Biol. Cell 21:4227-4239(2010) [PubMed] [Europe PMC] [Abstract]

"Functional polymorphism of the CK2alpha intronless gene plays oncogenic roles in lung cancer."
PLoS ONE 5:E11418-E11418(2010) [PubMed] [Europe PMC] [Abstract]

"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]

"Arsenic trioxide controls the fate of the PML-RARalpha oncoprotein by directly binding PML."
Science 328:240-243(2010) [PubMed] [Europe PMC] [Abstract]

"Initial characterization of the human central proteome."
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]

"Promyelocytic leukemia protein interacts with werner syndrome helicase and regulates double-strand break repair in gamma-irradiation-induced DNA damage responses."
Biochemistry (Mosc.) 76:550-554(2011) [PubMed] [Europe PMC] [Abstract]

"A Cullin3-KLHL20 Ubiquitin ligase-dependent pathway targets PML to potentiate HIF-1 signaling and prostate cancer progression."
Cancer Cell 20:214-228(2011) [PubMed] [Europe PMC] [Abstract]

"The role of PML in the control of apoptotic cell fate: a new key player at ER-mitochondria sites."
Cell Death Differ. 18:1450-1456(2011) [PubMed] [Europe PMC] [Abstract]

"The nuclear bodies inside out: PML conquers the cytoplasm."
Curr. Opin. Cell Biol. 23:360-366(2011) [PubMed] [Europe PMC] [Abstract]

"Mitogen-activated protein kinase extracellular signal-regulated kinase 2 phosphorylates and promotes Pin1 protein-dependent promyelocytic leukemia protein turnover."
J. Biol. Chem. 286:44403-44411(2011) [PubMed] [Europe PMC] [Abstract]

"PML isoforms I and II participate in PML-dependent restriction of HSV-1 replication."
J. Cell Sci. 124:280-291(2011) [PubMed] [Europe PMC] [Abstract]

"Role of promyelocytic leukemia protein in host antiviral defense."
J. Interferon Cytokine Res. 31:145-158(2011) [PubMed] [Europe PMC] [Abstract]

"Promyelocytic leukemia isoform IV confers resistance to encephalomyocarditis virus via the sequestration of 3D polymerase in nuclear bodies."
J. Virol. 85:13164-13173(2011) [PubMed] [Europe PMC] [Abstract]

"The SUMO protease SENP6 is a direct regulator of PML nuclear bodies."
Mol. Biol. Cell 22:78-90(2011) [PubMed] [Europe PMC] [Abstract]

"The role of PML in the nervous system."
Mol. Neurobiol. 43:114-123(2011) [PubMed] [Europe PMC] [Abstract]

"Entrapment of viral capsids in nuclear PML cages is an intrinsic antiviral host defense against Varicella-Zoster virus."
PLoS Pathog. 7:E1001266-E1001266(2011) [PubMed] [Europe PMC] [Abstract]

"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]

"The SUMO E3-ligase PIAS1 regulates the tumor suppressor PML and its oncogenic counterpart PML-RARA."
Cancer Res. 72:2275-2284(2012) [PubMed] [Europe PMC] [Abstract]

"MageA2 restrains cellular senescence by targeting the function of PMLIV/p53 axis at the PML-NBs."
Cell Death Differ. 19:926-936(2012) [PubMed] [Europe PMC] [Abstract]

"Role of the promyelocytic leukaemia protein in cell death regulation."
Cell Death Dis. 3:E247-E247(2012) [PubMed] [Europe PMC] [Abstract]

"Physical and functional interaction between PML and TBX2 in the establishment of cellular senescence."
EMBO J. 31:95-109(2012) [PubMed] [Europe PMC] [Abstract]

"PML regulates PER2 nuclear localization and circadian function."
EMBO J. 31:1427-1439(2012) [PubMed] [Europe PMC] [Abstract]

"Post-translational modifications of PML: consequences and implications."
Front. Oncol. 2:210-210(2012) [PubMed] [Europe PMC] [Abstract]

"Beta-catenin inhibits promyelocytic leukemia protein tumor suppressor function in colorectal cancer cells."
Gastroenterology 142:572-581(2012) [PubMed] [Europe PMC] [Abstract]

"Moloney murine leukemia virus integrase and reverse transcriptase interact with PML proteins."
J. Biochem. 152:161-169(2012) [PubMed] [Europe PMC] [Abstract]

"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. 287:23356-23367(2012) [PubMed] [Europe PMC] [Abstract]

"Contribution of the C-terminal regions of promyelocytic leukemia protein (PML) isoforms II and V to PML nuclear body formation."
J. Biol. Chem. 287:30729-30742(2012) [PubMed] [Europe PMC] [Abstract]

"The role of PML ubiquitination in human malignancies."
J. Biomed. Sci. 19:81-81(2012) [PubMed] [Europe PMC] [Abstract]

"PML promotes MHC class II gene expression by stabilizing the class II transactivator."
J. Cell Biol. 199:49-63(2012) [PubMed] [Europe PMC] [Abstract]

"A metabolic prosurvival role for PML in breast cancer."
J. Clin. Invest. 122:3088-3100(2012) [PubMed] [Europe PMC] [Abstract]

"Herpes simplex virus 1 ubiquitin ligase ICP0 interacts with PML isoform I and induces its SUMO-independent degradation."
J. Virol. 86:11209-11222(2012) [PubMed] [Europe PMC] [Abstract]

"BMK1 is involved in the regulation of p53 through disrupting the PML-MDM2 interaction."
Oncogene 32:3156-3164(2013) [PubMed] [Europe PMC] [Abstract]

"The epigenetic regulator UHRF1 promotes ubiquitination-mediated degradation of the tumor-suppressor protein promyelocytic leukemia protein."
Oncogene 32:3819-3828(2013) [PubMed] [Europe PMC] [Abstract]

"Requirement of PML SUMO interacting motif for RNF4- or arsenic trioxide-induced degradation of nuclear PML isoforms."
PLoS ONE 7:E44949-E44949(2012) [PubMed] [Europe PMC] [Abstract]

"PML tumor suppressor protein is required for HCV production."
Biochem. Biophys. Res. Commun. 430:592-597(2013) [PubMed] [Europe PMC] [Abstract]

"Selective inhibition of the NLRP3 inflammasome by targeting to promyelocytic leukemia protein in mouse and human."
Blood 121:3185-3194(2013) [PubMed] [Europe PMC] [Abstract]

"The adenoviral oncogene E1A-13S interacts with a specific isoform of the tumor suppressor PML to enhance viral transcription."
J. Virol. 87:965-977(2013) [PubMed] [Europe PMC] [Abstract]

"MOZ increases p53 acetylation and premature senescence through its complex formation with PML."
Proc. Natl. Acad. Sci. U.S.A. 110:3895-3900(2013) [PubMed] [Europe PMC] [Abstract]

"An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]

"The solution structure of the RING finger domain from the acute promyelocytic leukaemia proto-oncoprotein PML."
EMBO J. 14:1532-1541(1995) [PubMed] [Europe PMC] [Abstract]