FIGURE 9: Proposed model for stress-activated signal transduction pathways mediating cyclin C nuclear export and destruction following high oxidative stress.

Following high ROS stress cyclin C moves first to the nucleolus and then to the cytoplasm. Movement to the nucleolus requires Plc1 [55] whereas nucleolar export requires Slt2, Kdx1 activation and Cdk8 function [28, 34]. Under mild ROS stress the canonical CWI pathway is sufficient to transmit the stress signal to cyclin C leading to its nuclear export and destruction [28]. Under elevated ROS stress an additional MEKK (Ste11) is also required to transmit the stress signal via Mkk1/2 to cyclin C. Other sensors may also feed into the Ste11-Mkk1/2 pathway (see discussion for details).

28. Jin C, Strich R, Cooper KF (2014). Slt2p phosphorylation induces cyclin C nuclear-to-cytoplasmic translocation in response to oxidative stress. Mol Biol Cell 25(8): 1396-1407. http://dx.doi.org/10.1091/mbc.E13-09-0550

34. Cooper KF, Scarnati MS, Krasley E, Mallory MJ, Jin C, Law MJ, Strich R (2012). Oxidative-stress-induced nuclear to cytoplasmic relocalization is required for Not4-dependent cyclin C destruction. J Cell Sci 125(Pt 4): 1015-1026. http://dx.doi.org/10.1242/jcs.096479

55. Cooper KF, Mallory MJ, Strich R (1999). Oxidative stress-induced destruction of the yeast C-type cyclin Ume3p requires phosphatidylinositol-specific phospholipase C and the 26S proteasome. Mol Cell Biol 19(5): 3338-3348. http://www.ncbi.nlm.nih.gov/pubmed/?term=10207058