los/jun 
NGF 
r 
Fos/Jun 
binding site 
TH 
inactii^e 
Fos and Jun 
protein 
levels low 
Fos/Jun 
binding site 
TH 
active 
Fos/Jun 
synthesis 
induced 
by NGF 
lra?/jun? 
Fos/Jun 
binding site 
TH 
repressed 
Fra/Jun 
synthesis 
induced 
Model for a mechanism of control over a gene that may play a role in Parkinson's disease. The 
polypeptide hormone NGF (nerve growth factor) binds to receptors on the surface of nerve cells 
( neurons) and induces expression of the gene encoding tyrosine hydroxylase (TH). This enzyme 
carries out a critical step in the synthesis of the neurotransmitter dopamine, whose release by 
neurons transmits signals to neighboring cells. Thus NGF may indirectly control the neuron's 
signaling capacity. In the model, NGF induces synthesis of members of the Fos family of proteins, 
which form complexes with fun family proteins. These complexes bind to a regulatory element of 
the TH gene and stimulate TH expression. Later, proteins related to Fos — Fra's — are expressed 
and repress TH gene activity. A deficiency in dopamine production can lead to Parkinson's dis- 
ease and other neurological disorders. 
Research of Elena Gizang- Ginsberg and Edward Ziff. 
468 
