The
CPCA protein of the filamentous fungus Aspergillus nidulans is a member of the c-Jun-like transcriptional activator family. It acts as central
transcription factor of the cross-pathway regulatory network of
amino acid biosynthesis and is functionally exchangeable for the general control transcriptional activator Gcn4p of Saccharomyces cerevisiae. In contrast to GCN4, expression of
cpcA is strongly regulated by two equally important mechanisms with additive effects that lead to a fivefold increased
CPCA protein amount under
amino acid starvation conditions. One component of
cpcA regulation involves a transcriptional autoregulatory mechanism via a
CPCA recognition
element (CPRE) in the
cpcA promoter that causes a sevenfold increased
cpcA mRNA level when cells are starved for
amino acids. Point mutations in the CPRE cause a constitutively low
mRNA level of
cpcA and a halved
protein level when
amino acids are limited. Moreover, two upstream open reading frames (uORFs) in the 5' region of the
cpcA mRNA are important for a translational regulatory mechanism. Destruction of both short uORFs results in a sixfold increased
CPCA protein level under nonstarvation conditions and a 10-fold increase under
starvation conditions. Mutations in both the CPRE and uORF regulatory elements lead to an intermediate effect, with a low
cpcA mRNA level but a threefold increased
CPCA protein level independent of
amino acid availability. These data argue for a combined regulation of
cpcA that includes a translational regulation like that of yeast GCN4 as well as a transcriptional regulation like that of the mammalian jun and fos genes.