SOCS3 suppresses AP-1 transcriptional activity in neuroblastoma cells through inhibition of c-Jun N-terminal kinase

Tizong Miao; Dongsheng Wu; Yi Zhang; Xuenong Bo; Fang Xiao; Xinyu Zhang; Charalambos Magoulas; Maria Cristina Subang; Ping Wang; Peter M Richardson

doi:10.1016/j.mcn.2007.10.010

SOCS3 suppresses AP-1 transcriptional activity in neuroblastoma cells through inhibition of c-Jun N-terminal kinase

Mol Cell Neurosci. 2008 Feb;37(2):367-75. doi: 10.1016/j.mcn.2007.10.010. Epub 2007 Oct 30.

Authors

Tizong Miao¹, Dongsheng Wu, Yi Zhang, Xuenong Bo, Fang Xiao, Xinyu Zhang, Charalambos Magoulas, Maria Cristina Subang, Ping Wang, Peter M Richardson

Affiliation

¹ Centre for Neuroscience, Queen Mary's School of Medicine, University of London, E1 2AT, London, UK.

PMID: 18055217
DOI: 10.1016/j.mcn.2007.10.010

Abstract

Transduction and activation of an inducible form of STAT3 (signal transducer and activator of transcription) sufficed to increase VIP (vasoactive intestinal protein) mRNA concentrations in neuroblastoma cells. Overexpression of SOCS3 (suppressor of cytokine signaling) inhibited and mutant SOCS3 (with an inactivating point mutation in amino acid 25) enhanced the induction of VIP mRNA by CNTF (ciliary neurotrophic factor). Because mutant SOCS3 did not augment the increase in STAT transcriptional activity following CNTF stimulation, the enhancement by mutant SOCS3 of the actions of CNTF cannot be attributed to changes in STAT3 signaling. Mutant SOCS3 increased AP-1 (activator protein) transcriptional activity and JNK (c-Jun N-terminal kinase) activity and SOCS3 bound to the scaffolding protein, JNK-interacting protein-1: these observations provide a plausible explanation for the enhancement by mutant SOCS3 of the actions of CNTF. We conclude that endogenous SOCS3 inhibits AP-1 activity through blocking of JNK phosphorylation.

Publication types

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

MeSH terms

Adaptor Proteins, Signal Transducing / genetics
Adaptor Proteins, Signal Transducing / metabolism
Animals
Cell Line, Tumor
Ciliary Neurotrophic Factor / metabolism
Ciliary Neurotrophic Factor / pharmacology
Down-Regulation / genetics
Feedback, Physiological / genetics
Gene Expression Regulation / genetics
Humans
JNK Mitogen-Activated Protein Kinases / genetics
JNK Mitogen-Activated Protein Kinases / metabolism*
Mice
Neuroblastoma
Neurons / metabolism*
Phosphorylation
RNA, Messenger / metabolism
Rats
STAT3 Transcription Factor / genetics
STAT3 Transcription Factor / metabolism*
Suppressor of Cytokine Signaling 3 Protein
Suppressor of Cytokine Signaling Proteins / genetics
Suppressor of Cytokine Signaling Proteins / metabolism*
Transcription Factor AP-1 / genetics
Transcription Factor AP-1 / metabolism*
Transcription, Genetic / genetics*
Transcriptional Activation / genetics*
Vasoactive Intestinal Peptide / genetics
Vasoactive Intestinal Peptide / metabolism

Substances

Adaptor Proteins, Signal Transducing
Ciliary Neurotrophic Factor
MAPK8IP1 protein, human
RNA, Messenger
SOCS3 protein, human
STAT3 Transcription Factor
STAT3 protein, human
Suppressor of Cytokine Signaling 3 Protein
Suppressor of Cytokine Signaling Proteins
Transcription Factor AP-1
Vasoactive Intestinal Peptide
JNK Mitogen-Activated Protein Kinases