Table 1.

The effect of sumoylation on key elements of the hypoxic pathway.

Protein	Effect of SUMOylation	Details	Reference
HIF-1α	n.d.	SUMO1 is increased under hypoxia and directly interacts with HIF-1α	[101]
	Negative: ↑ degradation and/or ↓ activity	HIF-1α modification by RanBP2 inhibits HIF-1 activity	[105]
		PIASy-dependent modification and destabilization of HIF-1α is reversed by SENP1 (a HIF-1 target) under hypoxia	[106,107]
	Positive: ↑ protein stability and/or ↑ activity	Overexpression of SUMO1 or RSUME or Cbx4 stabilizes and/or activates HIF-1α.	[108,109,110,111]
HIF-2α	Negative: ↑ degradation	Sumoylation leads to VHL/RNF4-dependent ubiquitination and degradation of HIF-2α	[112]
ARNT	Negative: ↓ activity	Sumoylation under normoxia inhibits transcriptional capacity of ARNT and its interaction with PML	[113]
PHD3	↓ HIF-1 activity	PHD3 sumoylation represses HIF-1 transcriptional activity under hypoxia, without affecting its stability or PHD activity	[114,115]
FIH	↑ FIH degradation ↑ HIF-1 activity	FIH sumoylation under hypoxia promotes its degradation and enhances HIF-1α transcriptional activity	[116]
CBP/p300	↓ coactivator activity	Sumoylation of CBP or p300 recruits transcriptional repressors (Daxx/HDAC2 or HDAC6, respectively)	[117,118]
	↓ HIF-1 activity	De-sumoylation of p300 by SENP3 enhances HIF-1 activity	[70]
pVHL	↓ VHL interaction with HIFα ↑ HIF activity	pVHL sumoylation by PIASy inhibits its interaction with HIFα	[119]