Figure 6.

A mechanistic model for DHC2-mediated acquired TMZ resistance in MGMT-negative GBM cells. In MGMT-positive GBM cells, DHC2 is low or not expressed. MGMT mediates TMZ-induced DNA damage repair and results in TMZ-resistance. In MGMT-deficient GBM cells upon TMZ treatment, DHC2 is upregulated and mediated nuclear transportation of DNA repair proteins XPC and CBX5, further contributes to DNA damage repair and TMZ-resistance. Once DHC2 is depleted in MGMT-deficient GBM cells, XPC and CBX5 are degraded via a proteasome-dependent pathway, and result in persistent DNA damage and improvement of TMZ sensitivity.