PML suppresses IL-6-induced STAT3 activation by interfering with STAT3 and HDAC3 interaction

Masaya Kato; Ryuta Muromoto; Sumihito Togi; Masashi Iwakami; Yuichi Kitai; Shigeyuki Kon; Kenji Oritani; Tadashi Matsuda

doi:10.1016/j.bbrc.2015.04.040

PML suppresses IL-6-induced STAT3 activation by interfering with STAT3 and HDAC3 interaction

Biochem Biophys Res Commun. 2015 May 29;461(2):366-71. doi: 10.1016/j.bbrc.2015.04.040. Epub 2015 Apr 17.

Authors

Masaya Kato¹, Ryuta Muromoto¹, Sumihito Togi¹, Masashi Iwakami¹, Yuichi Kitai¹, Shigeyuki Kon¹, Kenji Oritani², Tadashi Matsuda³

Affiliations

¹ Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
² Department of Hematology and Oncology, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
³ Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan. Electronic address: tmatsuda@pharm.hokudai.ac.jp.

PMID: 25892518
DOI: 10.1016/j.bbrc.2015.04.040

Abstract

The promyelocytic leukemia protein PML acts as a tumor suppressor by forming transcription-regulatory complexes with a variety of repressor proteins. In the present study, we found that endogenous PML suppresses interleukin (IL)-6-induced gene expression as well as phosphorylation and transcriptional activation of STAT3 in hepatoma cells. We also found that PML-mediated suppression of IL-6-induced STAT3 activation by disrupting interactions between STAT3 and HDAC3. These results indicate that PML modulates IL-6-induced STAT3 activation and hepatoma cell growth by interacting with HDAC3.

Keywords: HDAC3; Hepatoma; IL-6; PML; STAT3; Transcriptional regulation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Hepatocellular / genetics
Carcinoma, Hepatocellular / metabolism*
Cell Line, Tumor
Gene Expression Regulation, Neoplastic
Histone Deacetylases / metabolism*
Humans
Interleukin-6 / metabolism*
Liver Neoplasms / genetics
Liver Neoplasms / metabolism*
Nuclear Proteins / metabolism*
Promyelocytic Leukemia Protein
Protein Interaction Maps
STAT3 Transcription Factor / genetics
STAT3 Transcription Factor / metabolism*
Transcription Factors / metabolism*
Transcriptional Activation
Tumor Suppressor Proteins / metabolism*

Substances

Interleukin-6
Nuclear Proteins
Promyelocytic Leukemia Protein
STAT3 Transcription Factor
Transcription Factors
Tumor Suppressor Proteins
PML protein, human
Histone Deacetylases
histone deacetylase 3