Faculty Collaboration Database

p38gamma MAPK cooperates with c-Jun in trans-activating matrix metalloproteinase 9. J Biol Chem 2010 May 14;285(20):15149-15158

Date

03/17/2010

Pubmed ID

20231272

Pubmed Central ID

PMC2865276

DOI

10.1074/jbc.M110.105429

Scopus ID

2-s2.0-77952058710 (requires institutional sign-in at Scopus site)   75 Citations

Abstract

Mitogen-activated protein kinases (MAPKs) regulate gene expression through transcription factors. However, the precise mechanisms in this critical signal event are largely unknown. Here, we show that the transcription factor c-Jun is activated by p38gamma MAPK, and the activated c-Jun then recruits p38gamma as a cofactor into the matrix metalloproteinase 9 (MMP9) promoter to induce its trans-activation and cell invasion. This signaling event was initiated by hyperexpressed p38gamma that led to increased c-Jun synthesis, MMP9 transcription, and MMP9-dependent invasion through p38gamma interacting with c-Jun. p38gamma requires phosphorylation and its C terminus to bind c-Jun, whereas both c-Jun and p38gamma are required for the trans-activation of MMP9. The active p38gamma/c-Jun/MMP9 pathway also exists in human colon cancer, and there is a coupling of increased p38gamma and MMP9 expression in the primary tissues. These results reveal a new paradigm in which a MAPK acts both as an activator and a cofactor of a transcription factor to regulate gene expression leading to an invasive response.

Author List

Loesch M, Zhi HY, Hou SW, Qi XM, Li RS, Basir Z, Iftner T, Cuenda A, Chen G

Authors

Guan Chen MD, PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Xiao-Mei Qi MD Associate Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Base Sequence
Cell Line, Transformed
Chromatin Immunoprecipitation
DNA Primers
Enzyme Activation
Humans
Matrix Metalloproteinase 9
Mice
Phosphorylation
Promoter Regions, Genetic
Protein Binding
Proto-Oncogene Proteins c-jun
Reverse Transcriptase Polymerase Chain Reaction
p38 Mitogen-Activated Protein Kinases