Figure 7. Interplay among sirtuin 1, H2A.Z, mTOR and c-Myc in prostate cancer cells.

(A) Under normal conditions, PCa cells display downregulation of SIRT1, thus, sirtuin 1 is unable to promote H2A.Z negative regulation directly, through its degradation, and indirectly, through mTOR pathway repression, leading to upregulation of c-Myc and other oncogenes. (B) When exposed to TSA, alone or combined with 5-aza-dC, or resveratrol, levels of sirtuin 1 are restored, leading to decreased levels of H2A.Z, partially due to mTOR pathway inhibition, but mostly via direct interaction between sirtuin 1 and the histone variant. Similarly, c-Myc levels decrease after treatment with those drugs.