Mechanistically, PCAF-mediated Akt1 acetylation enhanced Akt1 phosphorylation at both sites of Thr(308) and Ser(473) and further promoted the proliferation of glioblastoma cells.
In summary, our study identified the acetyltransferase PCAF as a positive cofactor of the Hh-Gli signaling pathway, leading us to propose PCAF as a candidate therapeutic target for the treatment of patients with medulloblastoma and glioblastoma.
To test this hypothesis, we determined the nucleotide sequence of the entire PCAF coding region in 37 astrocytic tumors (17 glioblastomas, 10 anaplastic astrocytomas, 7 low-grade astrocytomas, and 3 pilocytic astrocytomas).