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• W2029073059 endingPage "138" @default.
• W2029073059 startingPage "128" @default.
• W2029073059 abstract "MAPK (MAP kinase) phosphatase 3 (DUSP6/MKP3) is a cytosolic MKP (MAPK phosphatase) that regulates negatively ERK1/2 downstream to growth factor or apoptotic signaling. Transcription of DUSP6 gene is activated through the ERK1/2 pathway, which constitutes a feedback regulatory loop of ERK1/2 activation. However, the regulation of the function of the DUSP6/MKP3 protein is poorly known. MKP3 possesses a linker region between its N-terminal MAPK-binding domain and its C-terminal catalytic domain, which is conserved in the related MKPs DUSP7/MKPX and DUSP9/MKP4. In MKP3, the interdomain linker region contains a secondary ERK1/2 binding motif and an active nuclear export sequence. Here, we report that MKP3 protein levels are decreased in cells upon apoptotic stimulation in a caspase-dependent manner, and we identify a novel MKP3 regulatory mechanism mediated by the pro-apoptotic protease caspase-3, which involves the MKP3 interdomain linker region. Active caspase-3 targeted the linker region of MKP3 at several residues, rendering N-terminal and C-terminal MKP3 fragments that contain specific arrangements of nuclear export sequence and ERK1/2 interaction motifs. MKP3 caspase-3-generated fragments displayed differential properties to regulate ERK1/2 nuclear/cytosolic localization and activity. Our results indicate that caspase-3 cleavage of MKP3 down-regulates MKP3 full length and renders active MKP3 fragments, which may participate in novel regulatory pathways controlling the subcellular localization and activation of ERK1/2 during apoptosis." @default.
• W2029073059 created "2016-06-24" @default.
• W2029073059 creator A5018362030 @default.
• W2029073059 creator A5038879172 @default.
• W2029073059 creator A5045608955 @default.
• W2029073059 creator A5060743558 @default.
• W2029073059 date "2012-06-01" @default.
• W2029073059 modified "2023-10-15" @default.
• W2029073059 title "Caspase-3 Cleavage of DUSP6/MKP3 at the Interdomain Region Generates Active MKP3 Fragments That Regulate ERK1/2 Subcellular Localization and Function" @default.
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• W2029073059 doi "https://doi.org/10.1016/j.jmb.2012.04.004" @default.
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