Lesion-induced increase in nerve growth factor mRNA is mediated by c-fos

Journal Article · Tue May 01 00:00:00 EDT 1990 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.87.10.3899· OSTI ID:5451489

Hengerer, B; Lindholm, D; Heumann, R; Thoenen, H ^[1]; Ruether, U ^[2]; Wagner, E F ^[3]

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1. Max Planck Institute for Psychiatry, Munich (West Germany)
2. European Molecular Biology Laboratory, Heidelberg (West Germany)
3. Research Institute of Molecular Pathology, Vienna (Austria)

Lesion of the sciatic nerve caused a rapid increase in c-fos and c-jun mRNA that was followed about 2 hr later by an increase in nerve growth factor (NGF) mRNA. To evaluate whether the initial increase in c-fos mRNA is casually related to the subsequent increase in NGF mRNA, the authors performed experiments with fibroblasts of transgenic mice carrying an exogenous c-fos gene under the control of a metallothionein promoter. In primary cultures of these fibroblasts, CdCl{sub 2} evoked a rapid increase in exogenous c-fos mRNA, followed immediately by an increase in endogenous c-jun mRNA and with a slight delay by an increase in NGF mRNA. In fibroblasts of C3H control mice, CdCl{sub 2} had no effect on the mRNA levels of the protooncogenes c-fos and c-jun or of NGF. Additional evidence for a casual relationship between c-fos induction and the subsequent increase in NGF mRNA was obtained in cotransfection experiments. DNase I footprint experiments demonstrated that a binding site for transcription factor AP-1 in the first intron of the NGF gene was protected following c-fos induction. That this protected AP-1 site indeed was functional in the regulation of NGF expression was verified by deletion experiments and by a point mutation in the corresponding AP-1 binding region in the NGF promoter-chloramphenicol acetyltransferase reporter construct.

• OSTI ID: 5451489
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States) Vol. 87:10; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
BIOLOGICAL EFFECTS
CADMIUM CHLORIDES
CADMIUM COMPOUNDS
CADMIUM HALIDES
CHEMICAL ACTIVATION
CHLORIDES
CHLORINE COMPOUNDS
CONNECTIVE TISSUE CELLS
FIBROBLASTS
GENE REGULATION
GENES
GROWTH FACTORS
HALIDES
HALOGEN COMPOUNDS
MESSENGER-RNA
METALLOPROTEINS
METALLOTHIONEIN
MITOGENS
NERVES
NERVOUS SYSTEM
NUCLEIC ACIDS
ONCOGENES
ORGANIC COMPOUNDS
PROTEINS
RNA
SCIATIC NERVE
SOMATIC CELLS