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Accumulation of cytosolic succinate results the inhibition of the 2-oxoglutarate and Fe 2+ -dependent dioxygenases [prolyl hydroxylase domain (PDH) enzymes] responsible for the hydroxylation of the -subunit (HIF-1) of HIF-1

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Moreover, NK cells transfected with small interfering RNA (siRNA) against PRF1 showed dramatic decreases in PRF1 expression, coupled with downregulated NK cell cytotoxicity (data not shown), suggesting that perforin is an essential factor for determining NK cell killing capacity
