Fig. 1

Effect of caffeine on Cdc25 regulation in S. pombe. Cdc2- Cdc13 is regulated by Cdc25 and Wee1. Suppression of Cdc2 activity by the anaphase promoting complex (APC), facilitates mitotic exit and activation of the septation initiation network (SIN). Caffeine was initially thought to inhibit Rad3 activity resulting in DNA damage checkpoint override. More recent studies have identified the TORC1 complex as the major target of caffeine in vivo. TORC1 delays mitosis by negatively regulating Cdc25 and activating Wee1. TORC1 inhibition advances the timing of mitosis suggesting caffeine can modulate cell cycle progression by inhibiting this complex. Caffeine activates the Sty1 regulated environmental stress response (ESR) pathway, leading to partial Cdc25 inhibition by Srk1. Depending on the degree of activation, Sty1 can also modulate Cdc25 activity to advance mitosis. The Mad2 spindle checkpoint protein is involved in the regulation of the DNA replication checkpoint. Caffeine’s effect on cell cycle progression is partially inhibited by Mad2. *MTs (Microtubules). Green arrows indicate target activation. Red lines indicate inhibitory signalling