Abstract
Post-translational modification by small ubiquitin-like modifier (SUMO) plays an important role in the regulation of different signaling pathways and is involved in the formation of promyelocytic leukemia (PML) protein nuclear bodies following sumoylation of PML. In the present study, we found that IL-6 induces desumoylation of PML and dissociation between PML and SUMO1 in hepatoma cells. We also found that IL-6 induces mRNA expression of SENP1, a member of the SUMO-specific protease family. Furthermore, wild-type SENP1 but not an inactive SENP1 mutant restored the PML-mediated suppression of STAT3 activation. These results indicate that the IL-6 family of cytokines modulates STAT3 activation by desumoylation and inactivation PML through SENP1 induction.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Line, Tumor
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Cysteine Endopeptidases
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Endopeptidases / genetics
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Endopeptidases / metabolism*
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Humans
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Interleukin-6 / pharmacology
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Interleukin-6 / physiology*
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Mice
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Mutation
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Neoplasm Proteins / metabolism*
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Nuclear Proteins / metabolism*
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Promyelocytic Leukemia Protein
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Protein Processing, Post-Translational*
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RNA, Messenger / metabolism
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STAT3 Transcription Factor / metabolism*
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SUMO-1 Protein / metabolism*
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Transcription Factors / metabolism*
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Transcriptional Activation
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Tumor Suppressor Proteins / metabolism*
Substances
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Interleukin-6
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Neoplasm Proteins
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Nuclear Proteins
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Promyelocytic Leukemia Protein
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RNA, Messenger
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STAT3 Transcription Factor
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STAT3 protein, human
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SUMO-1 Protein
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SUMO1 protein, human
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Transcription Factors
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Tumor Suppressor Proteins
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PML protein, human
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Endopeptidases
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SENP1 protein, human
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Cysteine Endopeptidases