A novel nerve growth factor-responsive element in the stromelysin-1 (transin) gene that is necessary and sufficient for gene expression in PC12 cells.
Stromelysin-1 (ST-1) is an extracellular matrix metalloproteinase whose expression is transcriptionally regulated by nerve growth factor (NGF) in the PC12 rat pheochromocytoma cell line. In this paper, we define sequences in the proximal ST-1 promoter that contain a novel NGF-responsive element(s). We show that this cis-acting promoter element can bind nuclear proteins from both untreated and NGF-treated PC12 cells in a specific and saturable manner and is sufficient to confer NGF-inducibility to a heterologous promoter. At least a portion of this NGF-responsive element lies within a 12-base pair region between positions -241 and -229 of the ST-1 promoter and bears no sequence homology to other known transcriptional elements. In contrast to what has been reported for fibroblasts, an AP1 site centered around position -68 does not seem to be involved in the growth factor regulation of ST-1 in PC12 cells. These results suggest that the NGF regulation of ST-1 gene expression involves different promoter elements, and possibly different transcription factors, from that described for ST-1 induction by other growth factors.
deSouza
S
S
Department of Cell Biology & Anatomy, School of Medicine, Oregon Health Sciences University, Portland 97201, USA.
Lochner
J
J
Machida
C M
CM
Matrisian
L M
LM
Ciment
G
G
D000818:Animals; D001483:Base Sequence; D005786:Gene Expression Regulation; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000235:genetics*; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000494:pharmacology*; D016716:PC12 Cells; D011401:Promoter Regions, Genetic; D051381:Rats; D014162:Transfection
D009414:Nerve Growth Factors; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3