PML: Regulation and multifaceted function beyond tumor suppression

Cell & Bioscience

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

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]

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

ISSN: 2045-3701