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Table 1 Summary of factors and conditions involved in PML transcription, translation, alternative splicing and subcellular distribution

From: PML: Regulation and multifaceted function beyond tumor suppression

Type of regulation Extracellular stimuli Cellular regulators PML regulation Refs.
Transcription
  IFNs, TNFα Stat1 and Stat2/IRF3/IRF8 Upregulation of PML mRNA [29,30,31, 109]
  Oncogenic stress RAS/p53 Upregulation of PML mRNA [32, 33]
  Cytokine or hormone Stat3/Stat6 Downregulation of PML transcription [34]
Post-transcription
 Alternative splicing    Expression of different PML isoforms with distinct function [15, 20]
 Alternative splicing Herpes simplex virus-1 infection   Increase in cytoplasmic PML in response to viral infection [27]
 mRNA stability MicroRNAs delivered by colon cancer cell-derived microvesicles miR-1246 Targeting PML 3’-UTR for degradation [35]
Translation
  Oncogenic stress RAS/mTOR RAS/eIF4E Upregulation of Pml mRNA translation 5′-UTR in MEFs [36]
  TNFα p38/MNK1 Upregulation of PML mRNA translation via IRES [37]
Cytoplasmic PML regulation
  TGFβ TGFR Smad2/3 and SARA-mediated TGFβ signaling [8]
  Sulforaphane (SFN)   Increases in cytoplasmic PML proportion and nuclear NRF2 accumulation [28]
  PML 1272delAG and IVS3-1 G mutations   Increases in cytoplasmic PML proportion and inhibition of p53-mediated cell apoptosis [26]
NB formation
  Androgen   Decreases in PML NB formation [160]
  Ionizing radiation   Increases in PML NB formation [161]
  Cisplatin   Increases in PML NB formation [161]
  SFN   Decreases in PML NB formation [28]
  1. The abundance/activity of PML protein can be regulated at the level of transcription, alternative splicing, translation and subcellular distribution. The types of regulation are listed in the first column; the extracellular agent or stress that contributes to the PML regulation 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 regulation