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Literature summary for 3.4.22.B72 extracted from

  • Guo, C.; Hildick, K.L.; Luo, J.; Dearden, L.; Wilkinson, K.A.; Henley, J.M.
    SENP3-mediated deSUMOylation of dynamin-related protein 1 promotes cell death following ischaemia (2013), EMBO J., 32, 1514-1528.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
co-expression of Flag-tagged SENP3 with HA-tagged endoplasmic reticulum kinase PERK in HEK293 cells. Overexpression of HA-PERK causes loss of Flag-SENP3 in HEK293 cells, which is blocked by overexpression of the PERK inhibitor p58IPK Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
additional information PERK activation is required for decreased SENP3 activity, overexpression of HA-tagged PERK causes loss of Flag-tagged SENP3 activity in HEK293 cells via a mechanism dependent on PERK kinase activity, which is blocked by overexpression of the PERK inhibitor p58IPK Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
SUMOylated GTPase Drp1 + H2O Homo sapiens the substrate is a key target for SENP3-mediated deSUMOylation GTPase Drp1 + SUMO
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Organism

Organism UniProt Comment Textmining
Homo sapiens
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Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
SUMOylated GTPase Drp1 + H2O the substrate is a key target for SENP3-mediated deSUMOylation Homo sapiens GTPase Drp1 + SUMO
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SUMOylated GTPase Drp1 + H2O Drp1 is both SUMO-1 and SUMO-2/3 conjugated, SUMO-2/3-specific deSUMOylating by enzyme SENP3 Homo sapiens GTPase Drp1 + SUMO
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Synonyms

Synonyms Comment Organism
SENP3
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Homo sapiens
SUMO-2/3-specific protease
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Homo sapiens

General Information

General Information Comment Organism
malfunction downregulation of SENP3 increases Drp1 SUMO-2/3ylation and decreases its mitochondrial association, which reduces Drp1-dependent cytochrome c release via reduced mitochondrial fission and fragmentation. Depletion of enzyme SENP3 prolongs GTPase Drp1 SUMOylation, which suppresses Drp1-mediated cytochrome c release and caspase-mediated cell death. SENP3 levels recover following reoxygenation after oxygen/glucose deprivation allowing deSUMOylation of Drp1, which facilitates Drp1 localization at mitochondria and promotes fragmentation and cytochrome c release. RNAi knockdown of SENP3 protects cells from reoxygenation-induced cell death via a mechanism that requires Drp1 SUMOylation Homo sapiens
metabolism molecular mechanisms of SUMOylation in the cellular response to oxygen/glucose deprivation, overview Homo sapiens
additional information the SUMO-2/3-specific protease SENP3 is degraded during oxygen/glucose deprivation, proteolysis of SENP3 requires PERK kinase activity, in vitro modeling of ischaemia, via a pathway involving the unfolded protein response kinase PERK and the lysosomal enzyme cathepsin B, overview. SENP3 degradation does not involve ubiquitination Homo sapiens
physiological function enzyme SENP3-mediated deSUMOylation of dynamin-related protein 1 promotes cell death following ischaemia Homo sapiens