Figure 8. Proposed role of OLA1 in regulating protein synthesis and ISR.

(A) Model for eIF2-mediated translational control. In addition to the eIF2α phosphorylation mechanism that inhibits the regeneration of eIF2-GTP from eIF2-GDP by eIF2B, we propose that OLA1 directly binds eIF2 and converts eIF2-GTP to eIF2-GDP via its GTPase activity, thus providing a 2^nd mechanism that limits the availability of TC. (B,C) The balance between cancer cell survival vs. death in the presence of OLA1 (B) or its deficiency (C). Cancer cells within a solid tumor are under multiple chronic stresses and OLA1 has a function in lowering TC level as described in (A). When OLA1 is downregulated, a relatively higher level of TC would result in less active ISR-CHOP signaling and tilt the balance towards survival.