CDC25/YLR310C Summary Help

Standard Name CDC25
Systematic Name YLR310C
Alias CTN1
Feature Type ORF, Verified
Description Membrane bound guanine nucleotide exchange factor (GEF or GDP-release factor); indirectly regulates adenylate cyclase through activation of Ras1p and Ras2p by stimulating the exchange of GDP for GTP; required for progression through G1 (1 and see Summary Paragraph)
Also known as: CDC25'
Name Description Cell Division Cycle 2
Chromosomal Location
ChrXII:756993 to 752224 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Genetic position: 213 cM
Gene Ontology Annotations All CDC25 GO evidence and references
  View Computational GO annotations for CDC25
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Mutant phenotypes All CDC25 Phenotype evidence and references
Classical genetics
conditional
misexpression
reduction of function
Large-scale survey
conditional
null
reduction of function
repressible
Resources
interactions All CDC25 Interaction evidence and references
141 total interaction(s) for 87 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 21
  • Affinity Capture-RNA: 3
  • Affinity Capture-Western: 13
  • Biochemical Activity: 7
  • Reconstituted Complex: 8
  • Two-hybrid: 38
Genetic Interactions
  • Dosage Growth Defect: 1
  • Dosage Lethality: 3
  • Dosage Rescue: 25
  • Negative Genetic: 1
  • Phenotypic Enhancement: 2
  • Phenotypic Suppression: 6
  • Positive Genetic: 1
  • Synthetic Lethality: 2
  • Synthetic Rescue: 10
Resources
Expression Summary
histogram
Resources
Protein Information All CDC25 Protein evidence and references
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXII:756993 to 752224 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
SGD ORF map
Genetic position: 213 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates		 Chromosomal
Coordinates		 Most Recent Updates
Coordinates Sequence
CDS 1..4770 756993..752224 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000004301
SUMMARY PARAGRAPH for CDC25

In S. cerevisiae, growth and metabolism in response to nutrients, particularly glucose, is regulated to a large degree by the Ras/cyclic AMP (cAMP) pathway. cAMP is synthesized by the Cyr1p adenylate cyclase, which is activated by the Ras GTPases, Ras1p and Ras2p (reviewed in 3). In turn, these Ras proteins are activated by the Cdc25p guanine nucleotide-exchange factor (GEF), which stimulates Ras1p and Ras2p exchange of GDP for GTP (4, 5, 6). Through its role in regulating cAMP levels, Cdc25p is involved in the processes of fermentative growth, nonfermentative growth, cell cycling, sporulation, and cell size regulation (7, 8, 9, 10).

CDC25 encodes a 180 kDa plasma membrane-bound protein (11). The Cdc25p N-terminal domain contains an SH3 motif that binds adenylate cyclase and a cyclin destruction box motif that mediates Cdc25p ubiquitin-dependent degradation (12, 13). The C-terminal domain includes the catalytic domain and a membrane localization signal (14, 11). The Cdc25p C-terminus is sufficient for full biological activity and is essential for normal growth and viability (15, 14). Cdc25p is able to form homodimers as well as heterodimers with Sdc25p, another S. cerevisiae Ras-GEF. Mutational analysis suggests that Cdc25p intra- and inter-molecular interactions may be involved in regulation of Cdc25p activity (16, 1).

Cdc25p is also regulated by glucose; the presence of glucose in the media results in Cdc25p phosphorylation, which causes decreased protein association with membranes and decreased interaction with the Ras-GTPases (17). Mutation of potentially phosphorylated residues in this region leads to changes in the cellular response to glucose (18). Additionally, when glucose is replaced by a nonfermentable carbon source such as ethanol, overall levels of Cdc25p decrease slightly (19). Unrelated to carbon source, protein levels also drop when cells are exposed to various stresses such as heat and ethanol shocks and oxidative stress (20).

Deletion of CDC25 is lethal in some S. cerevisiae strains, but null mutants can be rescued by overexpression of SDC25 (4, 21, 19). In the W303 strain background, Cdc25p activity is not necessary for growth in glucose but essential for growth in galactose and non-fermentable carbon sources (8).

While the noncatalytic N-terminal domain of Cdc25p shares no similarity with proteins from other organisms, the C-terminal domain is homologous to the catalytic domain of many Ras-GEFs. Cdc25p homologs include murine Cdc25Mm, Drosophila Sos (Son of Sevenless), and human RASGRF1 (OMIM) and SOS1 (OMIM) (22, 23, and reviewed in 24).

Last updated: 2006-05-03

References cited on this page View Complete Literature Guide for CDC25
1) Chen RA, et al.  (2000) A role for the noncatalytic N terminus in the function of Cdc25, a Saccharomyces cerevisiae Ras-guanine nucleotide exchange factor. Genetics 154(4):1473-84
2) Hartwell LH, et al.  (1970) Genetic control of the cell-division cycle in yeast. I. Detection of mutants. Proc Natl Acad Sci U S A 66(2):352-9
3) Broach JR  (1991) RAS genes in Saccharomyces cerevisiae: signal transduction in search of a pathway. Trends Genet 7(1):28-33
4) Broek D, et al.  (1987) The S. cerevisiae CDC25 gene product regulates the RAS/adenylate cyclase pathway. Cell 48(5):789-99
5) Crechet JB, et al.  (1990) Enhancement of the GDP-GTP exchange of RAS proteins by the carboxyl-terminal domain of SCD25. Science 248(4957):866-8
6) Jones S, et al.  (1991) The CDC25 protein of Saccharomyces cerevisiae promotes exchange of guanine nucleotides bound to ras. Mol Cell Biol 11(5):2641-6
7) van Aelst L, et al.  (1991) Involvement of the CDC25 gene product in the signal transmission pathway of the glucose-induced RAS-mediated cAMP signal in the yeast Saccharomyces cerevisiae. J Gen Microbiol 137(2):341-9
8) Folch-Mallol JL, et al.  (2004) New roles for CDC25 in growth control, galactose regulation and cellular differentiation in Saccharomyces cerevisiae. Microbiology 150(Pt 9):2865-79
9) Dawes IW and Calvert GR  (1984) Initiation of sporulation in Saccharomyces cerevisiae. Mutations causing derepressed sporulation and G1 arrest in the cell division cycle. J Gen Microbiol 130(3):605-13
10) Belotti F, et al.  (2006) The N-terminal region of the Saccharomyces cerevisiae RasGEF Cdc25 is required for nutrient-dependent cell-size regulation. Microbiology 152(Pt 4):1231-42
11) Garreau H, et al.  (1996) Membrane-anchoring domains of Cdc25p, a Saccharomyces cerevisiae ras exchange factor. Biol Cell 86(2-3):93-102
12) Mintzer KA and Field J  (1999) The SH3 domain of the S. cerevisiae Cdc25p binds adenylyl cyclase and facilitates Ras regulation of cAMP signalling. Cell Signal 11(2):127-35
13) Kaplon T and Jacquet M  (1995) The cellular content of Cdc25p, the Ras exchange factor in Saccharomyces cerevisiae, is regulated by destabilization through a cyclin destruction box. J Biol Chem 270(35):20742-7
14) Lai CC, et al.  (1993) Influence of guanine nucleotides on complex formation between Ras and CDC25 proteins. Mol Cell Biol 13(3):1345-52
15) Camonis JH, et al.  (1986) Characterization, cloning and sequence analysis of the CDC25 gene which controls the cyclic AMP level of Saccharomyces cerevisiae. EMBO J 5(2):375-80
16) Camus C, et al.  (1997) Dimerization of Cdc25p, the guanine-nucleotide exchange factor for Ras from Saccharomyces cerevisiae, and its interaction with Sdc25p. Eur J Biochem 247(2):703-8
17) Gross E, et al.  (1992) Phosphorylation of the S. cerevisiae Cdc25 in response to glucose results in its dissociation from Ras. Nature 360(6406):762-5
18) Gross A, et al.  (1999) The N-terminal half of Cdc25 is essential for processing glucose signaling in Saccharomyces cerevisiae. Biochemistry 38(40):13252-62
19) Boy-Marcotte E, et al.  (1996) SDC25, a dispensable Ras guanine nucleotide exchange factor of Saccharomyces cerevisiae differs from CDC25 by its regulation. Mol Biol Cell 7(4):529-39
20) Wang L, et al.  (2004) Stress induces depletion of Cdc25p and decreases the cAMP producing capability in Saccharomyces cerevisiae. Microbiology 150(Pt 10):3383-91
21) Boy-Marcotte E, et al.  (1989) The C-terminal part of a gene partially homologous to CDC 25 gene suppresses the cdc25-5 mutation in Saccharomyces cerevisiae. Gene 77(1):21-30
22) Wei W, et al.  (1992) Identification of a mammalian gene structurally and functionally related to the CDC25 gene of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 89(15):7100-4
23) Simon MA, et al.  (1991) Ras1 and a putative guanine nucleotide exchange factor perform crucial steps in signaling by the sevenless protein tyrosine kinase. Cell 67(4):701-16
24) Quilliam LA, et al.  (1995) Guanine nucleotide exchange factors: activators of the Ras superfamily of proteins. Bioessays 17(5):395-404