protein-1 (AP-1) and AP-2, along with a variety of dimers of
the Jun and Fos family, are among several transcription factors with a
high affinity for the GC-rich putative binding and promoter regions
within PRNP . Activation by these transcription factors plays a
regulatory function in the brain [55]. These transcription factors
are operational as a consequence of JNK activation and c-Jun
phosphorylation, as well as the E4 promoter binding protein. Expression
of this binding protein depends on the intracellular levels of calcium
(Ca2+), together with many additional transcription factors involved in
phosphatase pathway regulation [56,57].
Interestingly, in experiments which induce the antisense silencing of
PrPC expression, the result is a phosphorylation of 4E
binding protein-1 (4EBP-1), a molecular event that causes the release of
eukaryotic translation initiation factor 4E (eIF4E) to proceed to
cap-dependent mRNA translation. This in turn causes an
autophagy-dependent cell death in glioma cells [58,59]. I.e.,