SIP1 IS A CATABOLITE REPRESSION-SPECIFIC NEGATIVE REGULATOR OF GAL GENE-EXPRESSION

The yeast Snflp kinase is required for normal expression of many genes involved in utilization of non-glucose carbon. Snflp is known to asso ciate with several proteins. One is Sip1p, a protein that becomes phos phorylated in the presence of Snflp and thus is a candidate Snflp kina se substrate. We have isolated the SIP1 gene as a multicopy suppressor of the gal83-associated defect in glucose repression of GAL gene expr ession. Multicopy SIP1 also suppressed the gal82-associated defect in glucose repression, suggesting that SIP1, GAL83 and GAL82 function int erdependently. Multicopy SIP1 gene reduces GAL1, GAL2, GAL7 and GAL10 gene expression three- to fourfold in cells grown in the presence of g lucose but has no effect in cells grown on nonrepressing carbon. Sip1- deletion cells exhibited a two- to threefold increase in GAL gene expr ession compared to wild-type cells when grown on glucose. These studie s show that SIP1 is a catabolite repression-specific negative regulato r of GAL gene expression. Northern analysis revealed two SIP1 transcri pts whose relative abundance changed with carbon source. Western blots revealed that Sip1p abundance is not markedly affected by carbon sour ce, suggesting that Sip1p may be regulated post-translationally.