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Table 2 Summary of signaling involved in PML post-translational modification

From: PML: Regulation and multifaceted function beyond tumor suppression

Type of post-translational modification Extracellular stimuli Cellular factors PML regulation Refs.
Sumoylation (site)
 K65/K160/K490 ND RanBP2 /Ubc9 Assembly of PML NBs [20, 38, 42, 43, 61, 162]
ND ZNF451-1 Increases in RNF4-mediated PML degradation [41]
 K65 and K160 As2O3, Tumorigenic adaptation PIAS1 Increases in CKII-mediated PML degradation [44]
 ND Cell cycle ND Oscillation of PML sumoylation status [163]
 K65/K160 As2O3   Sumoylation and sumoylation-mediated ubiquitination and degradation [51]
 ND TNFα HDAC7 Upregulation of sumoylation [45, 84]
 ND Thermal stress/Cellular stress SENP Desumoylation/NBs dynamic [44, 46,47,48,49,50]
 K65/K160 Viral infection LANA2 Upregulation of SUMO2-conjugated sumoylation [164]
 ND Epstein-Barr virus infection BZLF1 PML desumoylation and NB breakdown [124]
 ND Cytomegalovirus infection IE1 Disruption of PML NBs [126]
Phosphorylation (site)
 ND DNA damage ATR Nucleolar localization [6, 52, 67]
 S565 Osmotic stress/Cellular stress CKII PML degradation [73]
 S518 Hypoxia CDK1/2 Increases in KLHL20-meidated PML ubiquitination and degradation [58]
 ND Cell cycle Aurora kinase A PML hyper-phosphorylation [72]
 S403 and S505 EGF, oncogenic adaptation ERK2 Increases in Pin1-mediated PML degradation [70, 71]
 S527 and S530 As2O3 ERK1/2 Increases in PML sumoylation and PML-mediated apoptosis [69]
 S117 γ-irradiation Chk2 Increases in PML-mediated Apoptosis [66]
 S8, S36, and S38 DNA damage HIPK2 Increases in PML-mediated Apoptosis [68]
 S403 and T409 Mitogenic stimuli BMK1/ERK5 Inhibition of PML-mediated p21 suppression for cancer cell proliferation [165]
 S518 ND SCP1/SCP3 Blockade of CDK1/2-Pin1-KLHL20-PML regulatory loop and PML-mediated anti-angiogenesis [153]
Ubiquitination
  As2O3 E6AP PML degradation [55, 56]
  ND SIAH1 and SIAH2 PML degradation [57]
  ND UHRF1 PML degradation [166]
  Hypoxia KLHL20 PML degradation [58]
  As2O3 RNF4 Catalyzing sumoylation-dependent degradation, increase in PML NB formation [51, 53, 54]
  HSV-1 infection ICP0 PML degradation [125]
  As2O3 RNF111 (Arkadia) Catalyzing sumoylation-dependent degradation [59]
Isgylation
  Retinoic acid UBE1L/USP18 PML-RAR degradation [62, 63, 167]
Acetylation (site)
 K487 and K515 ND p300 Increases in PML sumoylation [74]
 K487 H2O2 Sirt1/Sirt5 Deacetylation of PML, increase in K490 sumoylation [75, 77]
 K487 ND Sirt1 Promotion of PML/PER2-induced BMAL1/CLOCK transcriptional activity [76]
Protein level regulation
  H2O2 Pin1 Decreases in Pin1-PML association and Pin1-mediated PML degradation [71]
  IGF-1, hypoxia Pin1 Increases in Pin1-PML association and Pin1-mediated PML degradation [108]
  1. Post-translational modification of PML controls multiple PML properties, such as protein-protein interaction, stability, NB formation and its ability to regulate transcription and apoptosis. The types of PML post-translational modification and modification sites are listed in the first column; the extracellular agent or stress that contributes to the PML post-translational modification is summarized in the second column; regulation factors that target or modify PML are shown in the third column and the final column describes effects of these regulatory factors on PML post-translational modification
  2. ND Not determined