WHI5/YOR083W Summary Help

Standard Name WHI5 1
Systematic Name YOR083W
Feature Type ORF, Verified
Description Repressor of G1 transcription; binds to SCB binding factor (SBF) at SCB target promoters in early G1; phosphorylation of Whi5p by the CDK, Cln3p/Cdc28p relieves repression and promoter binding by Whi5; periodically expressed in G1; WHI5 has a paralog, SRL3, that arose from the whole genome duplication (1, 2, 3, 4, 5 and see Summary Paragraph)
Name Description WHIskey 6
Chromosomal Location
ChrXV:479533 to 480420 | ORF Map | GBrowse
Gbrowse
Gene Ontology Annotations All WHI5 GO evidence and references
  View Computational GO annotations for WHI5
Molecular Function
Manually curated
Biological Process
Manually curated
High-throughput
Cellular Component
Manually curated
High-throughput
Regulators 1 genes
Resources
Classical genetics
null
Large-scale survey
null
Resources
236 total interaction(s) for 151 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 5
  • Affinity Capture-Western: 15
  • Biochemical Activity: 14
  • Protein-peptide: 1
  • Reconstituted Complex: 2
  • Two-hybrid: 2

Genetic Interactions
  • Dosage Growth Defect: 7
  • Dosage Lethality: 2
  • Dosage Rescue: 2
  • Negative Genetic: 112
  • Phenotypic Enhancement: 11
  • Phenotypic Suppression: 5
  • Positive Genetic: 32
  • Synthetic Growth Defect: 8
  • Synthetic Lethality: 2
  • Synthetic Rescue: 16

Resources
Expression Summary
histogram
Resources
Length (a.a.) 295
Molecular Weight (Da) 32,901
Isoelectric Point (pI) 6.76
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXV:479533 to 480420 | ORF Map | GBrowse
SGD ORF map
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..888 479533..480420 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 SGDIDS000005609
SUMMARY PARAGRAPH for WHI5

The WHI5 gene encodes a cell cycle regulated transcriptional repressor that inhibits both SBF (SCB-binding factor) and MBF (MCB-binding factor) mediated G1/S phase transcription (3, 4, 7). SBF and MBF complexes both contain the Swi6p transcriptional coactivator and either Swi4p (SBF) or Mbp1p (MBF), two sequence specific DNA binding proteins (reviewed in 8, 9). These complexes bind to SCB (Swi4/6-dependent cell cycle box) or MCB (Mlu1 cell cycle box) promoter sites to enhance the transcription of hundreds of genes, including additional transcription factors (10, 11). This results in the initiation of a complex transcriptional cascade required for coordinated cell cycle progression. Whi5p associates with G1-specific promoters through direct interactions with both SBF and MBF and affects the onset of G1/S phase transcription (34). The CDK/Cyclin complex, Cln3p/Cdc28p, a key regulator of both MBF- and SBF-dependent gene expression, hyperphosphorylates the WHI5 protein during late G1 causing it to dissociate from SBF and exit the nucleus where it remains until the end of mitosis (3, 4). Whi5p re-enters the nucleus after CDK activity is eliminated by the mitotic exit network (MEN).

A regulatory role was originally proposed for WHI5 when the complete set of deletion mutants was screened to identify novel genes that influence cell size and the subset of these that affect the critical cell size threshold required for passage through Start (1, 12). The whi5 deletion mutant was found to pass through Start at about half the size of congenic wild-type cells, thereby accelerating the G1/S phase transition (1, 12). Conversely, overexpression of WHI5 causes both a G1 delay and an increase in cell size in wild-type cells. In addition, deletion of WHI5 results in increased resistance to mating pheromone, a phenotype shared by other WHI mutants that regulate Start including: CLN3-1 (WHI1-1), whi3, and, vps51 (whi6) (1, 13, 14, 15).

Epistatic size interactions place WHI5 upstream of SBF, since the small cell size phenotype of the WHI5 deletion is dependent on the presence of functional copies of SWI4 and SWI6 (1, 4, 3). Deletion of WHI5 partially suppresses the increase in cell size caused by CLN3 inactivation and does not alter the small size phenotype of the CLN3-1 mutation; thus CLN3 functions upstream of WHI5 in keeping with other genetic and biochemical results (3, 4).

Whi5p functions in an equivalent regulatory pathway as that of the retinoblastoma (Rb) family proteins in metazoans and appears to be the budding yeast analog of Rb (reviewed in 16 and 6). The tumor suppressor Rb and related proteins function in quiescent cells and during the G1 phase of cycling cells to inhibit S phase entry through direct binding and inhibition of members of the E2F family of transcription factors. Mitogenic stimulation results in the inactivation of Rb proteins through, cyclinD/Cdk4 and cyclinE/Cdk2 dependent hyperphosphoryation, liberating E2F proteins and their heterodimeric partners to activate the transcriptional cascade required for timely S phase entry (4, 3 and references therein). Cln3p and Cln1p or Cln2p can mediate the stepwise phosphorylation of mammalian Rb when expressed in yeast and these functions can be complemented in yeast cells lacking G1 cyclins through the heterologous expression of human cyclins, D1 and E1 (17). In addition, mouse embryonic fibroblasts derived from mice with a triple knockout of Rb family members have a small cell size phenotype similar to what is observed when WHI5 is deleted (4 and references therein).

Last updated: 2006-08-24 Contact SGD

References cited on this page View Complete Literature Guide for WHI5
1) Jorgensen P, et al.  (2002) Systematic identification of pathways that couple cell growth and division in yeast. Science 297(5580):395-400
2) Spellman PT, et al.  (1998) Comprehensive identification of cell cycle-regulated genes of the yeast Saccharomyces cerevisiae by microarray hybridization. Mol Biol Cell 9(12):3273-97
3) de Bruin RA, et al.  (2004) Cln3 activates G1-specific transcription via phosphorylation of the SBF bound repressor Whi5. Cell 117(7):887-98
4) Costanzo M, et al.  (2004) CDK activity antagonizes Whi5, an inhibitor of G1/S transcription in yeast. Cell 117(7):899-913
5) Byrne KP and Wolfe KH  (2005) The Yeast Gene Order Browser: combining curated homology and syntenic context reveals gene fate in polyploid species. Genome Res 15(10):1456-61
6) Jorgensen P and Tyers M  (2004) How cells coordinate growth and division. Curr Biol 14(23):R1014-27
7) Pramila T, et al.  (2006) The Forkhead transcription factor Hcm1 regulates chromosome segregation genes and fills the S-phase gap in the transcriptional circuitry of the cell cycle. Genes Dev 20(16):2266-78
8) Breeden LL  (2003) Periodic transcription: a cycle within a cycle. Curr Biol 13(1):R31-8
9) Bahler J  (2005) Cell-cycle control of gene expression in budding and fission yeast. Annu Rev Genet 39:69-94
10) Iyer VR, et al.  (2001) Genomic binding sites of the yeast cell-cycle transcription factors SBF and MBF. Nature 409(6819):533-8
11) Simon I, et al.  (2001) Serial regulation of transcriptional regulators in the yeast cell cycle. Cell 106(6):697-708
12) Zhang J, et al.  (2002) Genomic scale mutant hunt identifies cell size homeostasis genes in S. cerevisiae. Curr Biol 12(23):1992-2001
13) Nash RS, et al.  (2001) Isolation and characterization of WHI3, a size-control gene of Saccharomyces cerevisiae. Genetics 157(4):1469-80
14) Nash R, et al.  (1988) The WHI1+ gene of Saccharomyces cerevisiae tethers cell division to cell size and is a cyclin homolog. EMBO J 7(13):4335-46
15) Cross FR  (1988) DAF1, a mutant gene affecting size control, pheromone arrest, and cell cycle kinetics of Saccharomyces cerevisiae. Mol Cell Biol 8(11):4675-84
16) Schaefer JB and Breeden LL  (2004) RB from a bud's eye view. Cell 117(7):849-50
17) Hatakeyama M, et al.  (1994) Collaboration of G1 cyclins in the functional inactivation of the retinoblastoma protein. Genes Dev 8(15):1759-71