Figure 7. Proposed model for the regulation of MGMT by HDAC8 and ADRM1.

HDAC8 regulates MGMT protein levels via its interaction with ADRM1. In TMZ-sensitive U87 cells, TMZ treatment causes the dissociation of HDAC8 from ADRM1, which results in the downregulation of MGMT together with accumulated DNA damage in cells. In TMZ-resistant T98G cells, the HDAC8 and ADRM1 interaction cannot be disrupted by TMZ treatment. The high level of MGMT expression confers resistance against TMZ treatment.