TRIM8 regulates Nanog via Hsp90β-mediated nuclear translocation of STAT3 in embryonic stem cells

Fumihiko Okumura; Akiko J Okumura; Masaki Matsumoto; Keiichi I Nakayama; Shigetsugu Hatakeyama

doi:10.1016/j.bbamcr.2011.05.013

TRIM8 regulates Nanog via Hsp90β-mediated nuclear translocation of STAT3 in embryonic stem cells

Biochim Biophys Acta. 2011 Oct;1813(10):1784-92. doi: 10.1016/j.bbamcr.2011.05.013. Epub 2011 Jun 2.

Authors

Fumihiko Okumura¹, Akiko J Okumura, Masaki Matsumoto, Keiichi I Nakayama, Shigetsugu Hatakeyama

Affiliation

¹ Department of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan.

PMID: 21689689
DOI: 10.1016/j.bbamcr.2011.05.013

Abstract

TRIM8 is a member of a protein family defined by the presence of a common domain structure composed of a tripartite motif including a RING-finger, one or two B-box domains and a coiled-coil motif. Here, we show that TRIM8 interacts with Hsp90β, which interacts with STAT3 and selectively downregulates transcription of Nanog in embryonic stem cells. Knock-down of TRIM8 increased phosphorylated STAT3 in the nucleus and also enhanced transcription of Nanog. These findings suggest that TRIM8 modulates translocation of phosphorylated STAT3 into the nucleus through interaction with Hsp90β and consequently regulates transcription of Nanog in embryonic stem cells.

Publication types

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

MeSH terms

Active Transport, Cell Nucleus / drug effects
Active Transport, Cell Nucleus / genetics
Animals
CHO Cells
Carrier Proteins / antagonists & inhibitors
Carrier Proteins / genetics
Carrier Proteins / metabolism
Carrier Proteins / physiology*
Cell Nucleus / drug effects
Cell Nucleus / metabolism*
Cells, Cultured
Cricetinae
Cricetulus
Embryonic Stem Cells / drug effects
Embryonic Stem Cells / metabolism*
Gene Expression Regulation, Developmental / drug effects
HSP90 Heat-Shock Proteins / metabolism
HSP90 Heat-Shock Proteins / physiology*
HeLa Cells
Homeodomain Proteins / genetics*
Homeodomain Proteins / metabolism
Humans
Mice
Models, Biological
Nanog Homeobox Protein
Nerve Tissue Proteins / antagonists & inhibitors
Nerve Tissue Proteins / genetics
Nerve Tissue Proteins / metabolism
Nerve Tissue Proteins / physiology*
Phosphorylation / drug effects
Protein Binding / drug effects
Protein Binding / physiology
Protein Transport / drug effects
Protein Transport / genetics
RNA, Small Interfering / pharmacology
STAT3 Transcription Factor / metabolism*

Substances

Carrier Proteins
HSP90 Heat-Shock Proteins
HSP90AB1 protein, human
Homeodomain Proteins
NANOG protein, human
Nanog Homeobox Protein
Nerve Tissue Proteins
RNA, Small Interfering
STAT3 Transcription Factor
STAT3 protein, human
TRIM8 protein, human