PML: Regulation and multifaceted function beyond tumor suppression

Hsu, Kuo-Sheng; Kao, Hung-Ying

doi:10.1186/s13578-018-0204-8

Cell & Bioscience

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]
K65/K160/K490	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]

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
ND Not determined

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ISSN: 2045-3701

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