Disease relevance of SIP4

• The DNA-binding domains of zinc cluster proteins Cat8 and Sip4 synthesized in Escherichia coli could interact in vitro with CSRE motifs of MDH2 [1].

High impact information on SIP4

• The sip1Delta sip2Delta gal83Delta strain is unable to derepress invertase, grows poorly on alternative carbon sources and fails to direct the phosphorylation of the Mig1 and Sip4 proteins in vivo [2].
• Indeed, deletion of individual beta-subunit genes causes distinct differences in the induction and phosphorylation of Sip4, strongly suggesting that the beta-subunits play an important role in substrate definition [2].
• Gal83 mediates the interaction of the Snf1 kinase complex with the transcription activator Sip4 [3].
• Gal83 interacts with Sip4 in two-hybrid assays in vivo, and bacterially expressed proteins bind in vitro [3].
• We present genetic evidence that Sip4 contributes to transcriptional activation by the CSRE and biochemical evidence that Sip4 binds to the CSRE [4].

Biological context of SIP4

• The positively acting regulatory genes CAT8 and SIP4 encode CSRE-binding proteins which contribute unequally to the regulated expression of a CSRE-dependent reporter gene (85% and 15%, respectively, under conditions of glucose derepression) [5].
• This finding agrees with the idea that phosphorylation by Cat1 may convert Sip4 into a functional activator [5].
• Contribution of Cat8 and Sip4 to the transcriptional activation of yeast gluconeogenic genes by carbon source-responsive elements [5].
• Deregulated variants of Cat8 and Sip4 are able to bind to the CSRE and allow glucose-insensitive gene activation, even in the absence of the other protein, arguing against the physiological significance of heterodimer formation [5].
• In a diploid disruption mutant of ORF J0922 coding for the transcriptional activator homologue, no colonies appeared before 10 days after transformation and then grew slowly [6].

Associations of SIP4 with chemical compounds

• Regulatory genes CAT8 and SIP4 both encode zinc-cluster proteins which can bind to CSRE motifs and activate target genes under conditions of glucose deprivation [7].
• The N terminus of the predicted 96-kDa SIP4 protein is homologous to the DNA-binding domain of the GAL4 family of transcriptional activators, with a C6 zinc cluster adjacent to a coiled-coil motif The C terminus contains a leucine zipper motif and an acidic region [8].

Regulatory relationships of SIP4

• The derepression deficiency of a CSRE-dependent reporter gene in a strain lacking the Cat1 (Snf1) protein kinase can be suppressed by Sip4 fused to a strong heterologous activation domain [5].

Other interactions of SIP4

• RT-PCR analyses revealed that the expression of SIP4 and HAP5, which are known to affect the expression of some of the gluconeogenic, TCA cycle and respiratory genes, were also increased under this condition [9].
• We show that Gal83 mediates the association of the kinase with Sip4, a Snf1-regulated transcription activator of gluconeogenic genes [3].
• Interaction of the Srb10 kinase with Sip4, a transcriptional activator of gluconeogenic genes in Saccharomyces cerevisiae [10].

Analytical, diagnostic and therapeutic context of SIP4

• Gel retardation assays provide evidence for a different binding affinity of Cat8 and Sip4 to at least some CSRE sequence variants [5].
• The Snf1 protein kinase interacts with Sip4 and regulates its phosphorylation and activator function in response to glucose limitation; however, evidence suggested that another kinase also regulates Sip4 [10].

References