The function, regulation and therapeutic implications of the tumor suppressor protein, PML

Cell & Bioscience

Table 1 PML post-translational modifications, regulators and effects of these modifications on PML protein levels

Regulators	Effect on PML	Target region/sites	References
KLHL20 (MLN4924), SIAH, E6AP, UHRF1	Down-regulates PML protein abundance by promoting ubiquitination		[120–124]
RNF4		SUMO-dependent	[118, 119]
KLHL39, USP11	Up-regulates PML protein by blocking ubiquitination		[125, 129]
MageA, HDAC7, PIAS1, SIRT1	Regulates PML SUMOylation	K65, K160, K490	[132–134]
MageA, HDAC7, PIAS1, SIRT1	Regulates PML SUMOylation	K490	[116, 131]
p300	Acetylation	K487, K515	[146]
SIRT1, SIRT5	De-acetylation, increase K490SUMOylation	K487	[9, 116]
Chk2	Phosphorylation	S117	[45]
CDK1/2		S518	[122]
ERK2		S403, S505	[142]
CK2 (Emodin)		S565^a	[143]
BMK1 (XMD9-92)		S8, S38	[144]
HIPK2		S403, T409	[145]
SCP1, SCP2 and SCP3	De-phosphorylation	S518	[128]
Pin1	Isomerization	pS518-P519	[122, 141, 142]

PML protein is controlled by several post-translational modifications, including ubquitination, SUMOylation, acetylation, phosphorylation and isomerization
^a Annotated as S517 in reference due to different PML isoform

ISSN: 2045-3701