The proteasome complex and the maintenance of pluripotency: sustain the fate by mopping up?

Table 2 Summary of proteasome inhibitors and their impact on pluripotency

Cell type	Concentration, inhibitor/time	Effect	Pluripotency marker	Reference
HFF/iPSC-derived fibroblast	250, 500 and 1,000 nM MG132/40 hours	No morphological change	Nondetectable	[21]
Fibroblasts	2 μM UK101/PD957	Complete inhibition of reprogramming	Nondetectable	[40]
MEFs	Low doses of MG132	Complete inhibition of reprogramming	Nondetectable	[32]
hESC-derived fibroblasts	250, 500 and 1,000 nM MG132/40 hours	No morphological change	Nondetectable	[21]
hESCs	125 nM MG132/40 hours	No effect	Significant downregulation of OCT4, SOX2, NANOG and TRA-1-60	[21]
	250 nM MG132/40 hours	Large patches of differentiated areas
	500 nM MG132/40 hours	Only differentiated cells
	1,000 nM MG132/40 hours	Detachment of undifferentiated cells
hESCs	62.5 nM MG132/24 hours	Downregulation of pluripotent markers and modified levels of specific germ-layer markers (upregulation of FGF5 and GATA4)	Significant downregulation of OCT4, NANOG, SOX2 and ZFP42	[34]
hESCs	2 μM UK101/PD957 for 4 days	Pluripotency diminished, less alkaline phosphatase positive colonies, upregulation of FGF5 and GATA4	Significant downregulation of TRA-1-81 and SSEA3	[40]

Application of distinct proteasome inhibitors on different cell types, the effect of inhibition and the influence on pluripotency-associated transcription factors. hESC, human embryonic stem cell; HFF, human neonatal foreskin fibroblast; iPSC, induced pluripotent stem cell; MEF, murine embryonic fibroblast.

ISSN: 1757-6512