ABSTRACT
Sit4p phosphatase is related to PP2A (Fig. 6.1) and was first defined in a hunt for mutations which restored HIS4 expression in the absence of the normal transcriptional activators (Arndt et al., 1989). sit4 mutations lead to alterations in the transcription of other genes, indicating that Sit4p may be important for transcriptional regulation, despite the fact that Sit4p appears to be largely excluded from the nucleus (Sutton et al., 1991). Sit4p is now one of the best understood yeast protein phosphatases, although interpretation of its functions is complicated because the effects of sit4 mutations are very strain-dependent. SIT4 is in principle an essential gene but the phenotype of sit4 deleted (sit4 ) and temperature-sensitive (Ts-) sit4 mutant strains is dependent on a polymorphic locus termed SSD1. In ssd1-d strains such as W303, sit4 is lethal and sit4-102 is Ts-; in SSD1-v strains such as S288C, sit4 is viable, conferring a slow growth phenotype, while sit4-102 is Ts+ (Sutton et al., 1991). SSD1-v alleles are dominant to ssd1-d and Ssd1p is a 1250-residue protein of unknown function but which may bind RNA (Uesono et al., 1997). In fact the SSD1 status of cells affects many different pathways (Stettler et al., 1993; Kikuchi et al., 1994; Uesono et al., 1994) and SSD1-v alleles ameliorate the defects of cells with a hyperactivated PKA pathway (Sutton et al., 1991; Wilson et al., 1991), deficient in the PKC1-MPK1 MAPK pathway or in ins1 mutants (Wilson et al., 1991). The temperature sensitivity of cells deficient in chitin synthase II is also suppressed by SSD1-v alleles (Bulawa, 1993), as is the slow growth defect of G1 cyclin-deficient strains (Cvrckova and Nasmyth, 1993). Although the common connection between these effects is undoubtedly protein phosphorylation, how Ssd1p comes to have such pleiotropic effects remains to be established.
