Cross-talk between klf4 and stat3 regulates axon regeneration

Song Qin, Yuhua Zou, Chun Li Zhang

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Cytokine-induced activation of signal transducer and activator of transcription 3 (STAT3) promotes the regrowth of damaged axons in the adult central nervous system (CNS). Here we show that KLF4 physically interacts with STAT3 upon cytokine-induced phosphorylation of tyrosine 705 (Y705) on STAT3. This interaction suppresses STAT3-dependent gene expression by blocking its DNA-binding activity. The deletion of KLF4 in vivo induces axon regeneration of adult retinal ganglion cells (RGCs) via Janus kinase (JAK)-STAT3 signalling. This regeneration can be greatly enhanced by exogenous cytokine treatment, or removal of an endogenous JAK-STAT3 pathway inhibitor called suppressor of cytokine signalling 3 (SOCS3). These findings reveal an unexpected cross-talk between KLF4 and activated STAT3 in the regulation of axon regeneration that might have therapeutic implications in promoting repair of injured adult CNS.

Original languageEnglish (US)
Article number2633
JournalNature Communications
Volume4
DOIs
StatePublished - 2013

Fingerprint

axons
STAT3 Transcription Factor
regeneration
Axons
Regeneration
transducers
Cytokines
Janus Kinases
Janus
central nervous system
Neurology
Central Nervous System
suppressors
deletion
phosphorylation
Phosphorylation
Retinal Ganglion Cells
gene expression
tyrosine
Gene expression

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Cross-talk between klf4 and stat3 regulates axon regeneration. / Qin, Song; Zou, Yuhua; Zhang, Chun Li.

In: Nature Communications, Vol. 4, 2633, 2013.

Research output: Contribution to journalArticle

@article{4680cf726eaa4f7b93afc651fb3115c4,
title = "Cross-talk between klf4 and stat3 regulates axon regeneration",
abstract = "Cytokine-induced activation of signal transducer and activator of transcription 3 (STAT3) promotes the regrowth of damaged axons in the adult central nervous system (CNS). Here we show that KLF4 physically interacts with STAT3 upon cytokine-induced phosphorylation of tyrosine 705 (Y705) on STAT3. This interaction suppresses STAT3-dependent gene expression by blocking its DNA-binding activity. The deletion of KLF4 in vivo induces axon regeneration of adult retinal ganglion cells (RGCs) via Janus kinase (JAK)-STAT3 signalling. This regeneration can be greatly enhanced by exogenous cytokine treatment, or removal of an endogenous JAK-STAT3 pathway inhibitor called suppressor of cytokine signalling 3 (SOCS3). These findings reveal an unexpected cross-talk between KLF4 and activated STAT3 in the regulation of axon regeneration that might have therapeutic implications in promoting repair of injured adult CNS.",
author = "Song Qin and Yuhua Zou and Zhang, {Chun Li}",
year = "2013",
doi = "10.1038/ncomms3633",
language = "English (US)",
volume = "4",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Cross-talk between klf4 and stat3 regulates axon regeneration

AU - Qin, Song

AU - Zou, Yuhua

AU - Zhang, Chun Li

PY - 2013

Y1 - 2013

N2 - Cytokine-induced activation of signal transducer and activator of transcription 3 (STAT3) promotes the regrowth of damaged axons in the adult central nervous system (CNS). Here we show that KLF4 physically interacts with STAT3 upon cytokine-induced phosphorylation of tyrosine 705 (Y705) on STAT3. This interaction suppresses STAT3-dependent gene expression by blocking its DNA-binding activity. The deletion of KLF4 in vivo induces axon regeneration of adult retinal ganglion cells (RGCs) via Janus kinase (JAK)-STAT3 signalling. This regeneration can be greatly enhanced by exogenous cytokine treatment, or removal of an endogenous JAK-STAT3 pathway inhibitor called suppressor of cytokine signalling 3 (SOCS3). These findings reveal an unexpected cross-talk between KLF4 and activated STAT3 in the regulation of axon regeneration that might have therapeutic implications in promoting repair of injured adult CNS.

AB - Cytokine-induced activation of signal transducer and activator of transcription 3 (STAT3) promotes the regrowth of damaged axons in the adult central nervous system (CNS). Here we show that KLF4 physically interacts with STAT3 upon cytokine-induced phosphorylation of tyrosine 705 (Y705) on STAT3. This interaction suppresses STAT3-dependent gene expression by blocking its DNA-binding activity. The deletion of KLF4 in vivo induces axon regeneration of adult retinal ganglion cells (RGCs) via Janus kinase (JAK)-STAT3 signalling. This regeneration can be greatly enhanced by exogenous cytokine treatment, or removal of an endogenous JAK-STAT3 pathway inhibitor called suppressor of cytokine signalling 3 (SOCS3). These findings reveal an unexpected cross-talk between KLF4 and activated STAT3 in the regulation of axon regeneration that might have therapeutic implications in promoting repair of injured adult CNS.

UR - http://www.scopus.com/inward/record.url?scp=84886074999&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84886074999&partnerID=8YFLogxK

U2 - 10.1038/ncomms3633

DO - 10.1038/ncomms3633

M3 - Article

VL - 4

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 2633

ER -