CLN3-ASSOCIATED KINASE-ACTIVITY IN SACCHAROMYCES-CEREVISIAE IS REGULATED BY THE MATING FACTOR PATHWAY

The Saccharomyces cerevisiae cell cycle is arrested in G(1) phase by t he mating factor pathway. Genetic evidence has suggested that the G1 c yclins Cln1, Cln2, and Cln3 are targets of this pathway whose inhibiti on results in G(1) arrest, Inhibition of Cln1- and Cln2-associated kin ase activity by the mating factor pathway acting through Far1 has been described, Here we report that Cln3-associated kinase activity is inh ibited by mating factor treatment, with dose response and timing consi stent with involvement in cell cycle arrest, No regulation of Cln3-ass ociated kinase was observed in a fus3 kss1 strain deficient in mating factor pathway mitogen-activated protein (MAP) kinases, Inhibition occ urs mainly at the level of specific activity of Cln3-Cdc28 complexes, Inhibition of the C-terminally truncated Cln3-1-associated kinase is n ot observed; such truncations were previously identified genetically a s causing resistance to mating factor-induced cell cycle arrest, Regul ation of Cln3-associated kinase specific activity by mating factor tre atment requires Farl, Overexpression of Farl restores inhibition of C- terminally truncated Cln3-1-associated kinase activity, G(2)/M-arreste d cells are unable to regulate Cln3-associated kinase, possibly becaus e of cell cycle regulation of Farl abundance, Inhibition of Cln3-assoc iated kinase activity by the mating factor pathway may allow this path way to block the earliest step in normal cell cycle initiation, since Cln3 functions as the most upstream G(1)-acting cyclin, activating tra nscription of the G(1) cyclins CLN1 and CLN2 as well as of the S-phase cyclins CLB5 and CLB6.