. 2020 Apr 28;77(20):4049–4067. doi: 10.1007/s00018-020-03525-8

Table 3.

Different PTMs of CREB and their functional relevance

Modification	aa residue in CREB	CREB activity	Mechanism	Species	References
Acetylation	K136	Increased	Recruitment of CBP/p300	M, 3T3-L	[140]
	K136	Increased	Deacetylation by SirT1	H, HEK293T	[141]
	K91, 94, 136	Decreased^a	Acetylation by CBP/p300	R, F9; Mo, COS-7	[142]
	n/a	Increased	HDAC9 regulating CREB mRNA	H, HuH7	[143]
	K136	Increased	CREB acetylation increased by low glucose	M, hippocampal cells	[144]
Ubiquitination	K48-linked^b	Decreased	TRAF3 increasing ubiquitination	M, B cells	[145]
	n/a	Decreased	MTUS1 deubiquitinating CREB	H, THP-1 cells	[146]
	K48-linked^c	Decreased	Hypoxia-mediated ubiquitination	M, NIH3T3 cells	[147]
	n/a	Decreased	H₂O₂-induced ubiquitination	D, in vivo	[148]
	n/a^c	Decreased	PDGF-stimulated phosphorylation of S103/S107	R, pulmonary artery	[149]
	n/a	Decreased	Hypoxia-mediated loss of PP1 activity	H, CaCo-2 cells	[150]
	n/a	Decreased	Hypoxia-mediated ubiquitination	H, HeLa; BT, T84	[151]
SUMOylation	K271, K290	Increased	PIAS1-induced modification with SUMO-1	H, HEK293T	[152]
	K285, K304	Increased	Hypoxia mediated by SUMO-1	H, HeLa; BT, T84	[151]
	K285, K304	Increased	Hypoxia mediated by SUMO-1,2,3	M, NIH3T3 cells	[147]
O glycosylation	S40, T228	Decreased	Elevated CRTC/TORC interaction	R, neuronal cells	[153]
	n/a	Decreased	Nuclear import under high glucose	H, HuH7	[154]
	T256, S260	Decreased	Disrupted interaction with TAFII130	R, brain	[155]
	n/a	Decreased	Iron-induced decreased levels of O-GlcNAcylated	M, 3T3-L	[156]
phosphorylation (not in KID)	S270/S271	Decreased	DNA damage	H, HeLa; H, HEK293T	[157, 158]
phosphorylation (not in KID)	S271	Increased	Genotoxic stress	H, SH-SY5Y; H K562	[158]

Species: M mouse, H human, R rat, D dog, BT cow, Mo monkey; n/a not analyzed

^aTriple mutants only; in single mutants, no changes were observed; enhanced CREB-mediated gene expression, when inhibition of histone deacetylase activity by trichostatin A

^bPolyubiquitinated chain, CREB aa not assigned

^cPolyubiquitinated chain and monoubiquitination, presumably CREB-K330 or K339