Human Neutrophil Lactoferrin trans-Activates the Matrix Metalloproteinase 1 Gene through Stress-activated MAPK Signaling Modules

Sang M. Oh, Dae Hyun Hahm, Ik Hwan Kim, Sang Y. Choi

Research output: Contribution to journalArticle

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Abstract

It has been proposed that human neutrophil lactoferrin (Lf) could be involved in gene expression as a DNA-binding protein after its translocation into the nucleus. However, the molecular basis of Lf action has not been defined, and Lf-regulated target genes have not been identified. We report here that overexpressed Lf functions as a specific trans-activator of matrix metalloproteinase 1 (MMP1) gene, and that induction of this AP-1-responsive gene is mediated via the stress-activated MAPK signaling modules. Transactivation of the MMP1 promoter by overexpressed Lf requires the presence of an AP-1 binding site. In gel shift experiments, Lf did not interact directly with AP-1-containing fragments of the MMP1 promoter. However, nuclear extracts from Lf-expressing cells contained increased levels of proteins that bound to AP-1 elements. This Lf-induced AP-1 DNA binding activity was reduced by a p38 MAPK inhibitor. Inhibitors of the MEK kinases had little effect on Lf-induced AP-1. However, expression of dominant-negative MKK4 or JNK1 inhibited Lf-induced gene expression. The JNK activity stimulated by Lf correlates with the enhanced AP-1 binding ability. These findings demonstrate that the Lf-induced activation of AP-1 is mediated via JNK and p38 MAPK pathways.

Original languageEnglish
Pages (from-to)42575-42579
Number of pages5
JournalJournal of Biological Chemistry
Volume276
Issue number45
DOIs
Publication statusPublished - 2001 Nov 9

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Matrix Metalloproteinase 1
Lactoferrin
Neutrophils
Genes
Transcription Factor AP-1
p38 Mitogen-Activated Protein Kinases
Gene expression
MAP Kinase Kinase Kinases
Gene Expression
Trans-Activators
DNA-Binding Proteins
Transcriptional Activation
Gels
Chemical activation
Binding Sites

ASJC Scopus subject areas

  • Biochemistry

Cite this

Human Neutrophil Lactoferrin trans-Activates the Matrix Metalloproteinase 1 Gene through Stress-activated MAPK Signaling Modules. / Oh, Sang M.; Hahm, Dae Hyun; Kim, Ik Hwan; Choi, Sang Y.

In: Journal of Biological Chemistry, Vol. 276, No. 45, 09.11.2001, p. 42575-42579.

Research output: Contribution to journalArticle

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