High impact information on YLL017W

• The 3'-terminal part of SCD25, a gene of S. cerevisiae structurally related to CDC25, can suppress the requirement for CDC25 [1].
• Partially purified preparations of the carboxy-terminal domain of the SCD25 gene product enhanced the exchange rate of guanosine diphosphate (GDP) to guanosine triphosphate (GTP) of pure RAS2 protein by stimulating the release of GDP [1].
• Mutations of Ha-ras p21 that define important regions for the molecular mechanism of the SDC25 C-domain, a guanine nucleotide dissociation stimulator [2].
• Using purified RAS proteins, we have found that the SDC25-stimulated conversion of RAS from the GDP-bound inactive state to the GTP-bound active state was severely impaired by amino acid substitutions at positions 80-81 [3].
• Specifically, SDC25 C domain functions as an exchange factor for cellular Ras proteins in CHO cells [4].

Biological context of YLL017W

• The SDC25 gene was found to be dispensable for cell growth under usual conditions [5].
• The SDC25 gene is located on the chromosome XII close to the centromere [5].
• The complementing part of this fragment contains a truncated open reading frame (ORF) corresponding to the 3' end of a gene we named SCD25 [6].
• Biochemical evidence was obtained, showing that in the presence of the functional target of RAS, the adenylyl cyclase, the effects of SDC25 C-domain and the catalytic domain of GTPase-activating protein are antagonistic [7].
• The temperature-sensitive phenotype can be rescued by CDC25 itself, as well as by a plasmid containing a truncated SDC25 gene [8].

Anatomical context of YLL017W

• Determination of GEF effects showed that in cell membrane the Cdc25p dependent activity on Ras2p was predominant over that of Sdc25p [9].
• The SDC25 C-domain was able to stimulate the adenylyl cyclase activity of membranes from RAS2 cdc25 strains [7].
• We have demonstrated that the SDC25 C-terminus domain promotes GTP binding to Ras p21 in CHO cells [10].
• In addition, coexpression of SDC25 C domain overcomes the inhibition of proliferation of NIH 3T3 cells caused by Ha-Ras Asn-17 [4].

Associations of YLL017W with chemical compounds

• Guanine Exchange Factor (GEF) activity for Ras proteins has been associated with a conserved domain in Cdc25p, Sdc25p in Saccharomyces cerevisiae and several other proteins recently found in other eukaryotes [11].
• SDC25, a dispensable Ras guanine nucleotide exchange factor of Saccharomyces cerevisiae differs from CDC25 by its regulation [12].
• We also show that the two genes are differentially regulated: SDC25 is not transcribed at a detectable level in growth conditions when glucose is the carbon source [12].

Physical interactions of YLL017W

• These results strongly suggest that the residues R80 and N81 are situated in or closely associated with the Ras2p specific site binding Sdc25p [13].

Regulatory relationships of YLL017W

• In contrast with the C-terminal part, the complete SDC25 gene was found not to suppress the CDC25 gene defect [5].
• Our results indicate that the SDC25 C-domain activates adenylyl cyclase by rapidly recycling the active RAS2. or RAS1.GTP complex from the respective GDP complex [7].

Other interactions of YLL017W

• We demonstrate that the GEF domain of Sdc25p is closely related to that of Cdc25p [11].
• We have introduced single and double amino acid substitutions at positions 80-83 of the RAS2 gene, and we have investigated the interaction of the corresponding proteins with a yeast GDP dissociation stimulator (SDC25 C-domain) [3].
• We have analyzed the function of this region and the effect of its farnesylation with respect to the action of the GDP/GTP exchange factors (GEFs) Cdc25p and Sdc25p and the target adenylyl cyclase [9].

Analytical, diagnostic and therapeutic context of YLL017W

• Retention phenomena occurring on gel-filtration chromatography hindered the use of highly purified Sdc25p-C to study the formation of stable complexes with Ras2p [13].

References