The IL-6 family of cytokines modulates STAT3 activation by desumoylation of PML through SENP1 induction.
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.
Ohbayashi
Norihiko
N
Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-Ku Kita 12 Nishi 6, Sapporo 060-0812, Japan.
Kawakami
Shiho
S
Muromoto
Ryuta
R
Togi
Sumihito
S
Ikeda
Osamu
O
Kamitani
Shinya
S
Sekine
Yuichi
Y
Honjoh
Tsutomu
T
Matsuda
Tadashi
T
D000818:Animals; D045744:Cell Line, Tumor; D003546:Cysteine Endopeptidases; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D009154:Mutation; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D000071156:Promyelocytic Leukemia Protein; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D025842:SUMO-1 Protein / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D015850:Interleukin-6; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D025842:SUMO-1 Protein; C495501:SUMO1 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; D010450:Endopeptidases; C404512:SENP1 protein, human; D003546:Cysteine Endopeptidases