CDC53/YDL132W Summary Help

Standard Name CDC53 1
Systematic Name YDL132W
Feature Type ORF, Verified
Description Cullin; structural protein of SCF complexes (which also contain Skp1p, Cdc34p, Hrt1p and an F-box protein) involved in ubiquitination; SCF promotes the G1-S transition by targeting G1 cyclins and the Cln-CDK inhibitor Sic1p for degradation (1, 2, 3, 4 and see Summary Paragraph)
Name Description Cell Division Cycle
Chromosomal Location
ChrIV:224304 to 226751 | ORF Map | GBrowse
Gbrowse
Genetic position: -81 cM
Gene Ontology Annotations All CDC53 GO evidence and references
  View Computational GO annotations for CDC53
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 2 genes
Resources
Classical genetics
conditional
null
overexpression
repressible
Large-scale survey
conditional
null
overexpression
reduction of function
repressible
Resources
230 total interaction(s) for 76 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 53
  • Affinity Capture-RNA: 1
  • Affinity Capture-Western: 74
  • Biochemical Activity: 3
  • Co-fractionation: 1
  • Co-purification: 4
  • Reconstituted Complex: 32
  • Two-hybrid: 22

Genetic Interactions
  • Dosage Lethality: 7
  • Dosage Rescue: 7
  • Negative Genetic: 2
  • Phenotypic Enhancement: 1
  • Phenotypic Suppression: 4
  • Synthetic Growth Defect: 6
  • Synthetic Lethality: 11
  • Synthetic Rescue: 2

Resources
Expression Summary
histogram
Resources
Length (a.a.) 815
Molecular Weight (Da) 93,943
Isoelectric Point (pI) 8.78
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrIV:224304 to 226751 | ORF Map | GBrowse
SGD ORF map
Genetic position: -81 cM
Last Update Coordinates: 1996-07-31 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..2448 224304..226751 1996-07-31 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 SGDIDS000002290
SUMMARY PARAGRAPH for CDC53

CDC53 encodes a scaffolding subunit or cullin for multiple related RING-type E3 ubiquitin-ligase complexes, generically referred to as Skp1-Cullin-F-box (SCF) ubiquitin protein ligases (5). SCF-mediated ubiquitination involves three sequential enzymatic steps: ATP-dependent activation of ubiquitin through the formation of a high-energy thioester linkage with a ubiquitin-activating enzyme (E1); transfer of the activated ubiquitin to a ubiquitin-conjugating enzyme (E2); and the E2-catalyzed transfer of activated ubiquitin to a specific lysine residue(s) of the target protein, aided by substrate-specific components of SCF-ubiquitin ligase complexes (E3s). This sequence is repeated until multiple chains of ubiquitin are attached, thereby marking the protein for rapid degradation by the 26S proteasome (reviewed in 6 and 7).

SCF ubiquitin protein ligase complexes function as target recognition modules that regulate cell cycle progression and signal transduction by bringing E2s and substrates into close proximity, thereby facilitating substrate polyubiquitination (reviewed in 7, 8 and 9). SCF ubiquitin-ligase complexes are composed of several shared subunits including Skp1p, an adaptor protein that binds and recruits a variety of F-box containing proteins (10, 11); Cdc53p, a cullin family member that recruits the ubiquitin conjugating enzyme Cdc34p to Skp1p/F-box proteins (5, 4, 1); Hrt1p, a RING-H2 domain protein that stimulates ubiquitin ligase activity (3, 12); and Cdc34p, a ubiquitin-conjugating enzyme that catalyzes the transfer of activated ubiquitin to the target protein (13, 2, 11). In addition, to these shared subunits, SCF complexes also contain one of several unique F-box motif containing proteins, including Cdc4p, Grr1p, Met30p, Dia2p, or Saf1p, that function as substrate specific adaptors or specificity determinants recruiting multiply phosphorylated substrates to the SCF core complex (reviewed in 7, 14 and 15). Multiple substrates have been identified for specific SCF-F-box protein complexes. SCF-Cdc4p facilitates the polyubiquitination of Sic1p (2, 11), Far1p (16, 17), Cdc6p (18, 19), Clb6p (20) and Hac1p (21); substrates of SCF-Grr1p include Cln1p, Cln2p (4, 22), Gic1p, and Gic2p (23); substrates of SCF-Met30p include Met4p (24) and Swe1p (25); SCF-Dia2p polyubiquitinates Tec1p (26); and SCF-Saf1p polyubiquitinates Aah1p (27). The F-box proteins CDC4, GRR1 and MET30 are also intrinsically unstable and are able to catalyze their own SCF-mediated ubiquitination and destruction via an autocatalytic mechanism proposed to facilitate rapid switching among multiple SCF complexes (28, 29). Finally, a subcomplex containing Cdc53p and Hrt1p functions as a ubiquitin-ligase module capable of activating the autoubiquitination of Cdc34p (30, 3).

cdc53 was originally identified as a cell division cycle (CDC) mutant that arrests at the G1/S phase transition with multiple elongated buds and unreplicated DNA, similar to cdc4, cdc34 and hrt1 mutants (1, 12). Cln2p and Sic1p are stabilized in both cdc53-1 and cdc34-2 mutants arrested at the restrictive temperature (10, 31); overexpression of either CLN2 or CLN3 in cdc53-1 or cdc34-2 mutants exacerbates this phenotype, impairing colony formation at the permissive temperature (4, 32). Deletion of the CDK inhibitor SIC1 alters the terminal phenotype of cdc53, cdc34 and cdc4 mutants, resulting in cells that now arrest at the G2/M phase transition of the cell cycle with replicated DNA and a single round bud (23, 31).

Cdc53p is regulated by neddylation, a ubiquitin-like modification in which the protein Rub1p (NEDD8 in higher eukaryotes) is conjugated to its substrate (reviewed in 33). Neddylation of cullins has been proposed to positively regulate E3 ligase activity and assembly of SCF complexes (34, 35, 36).

Cdc53p is evolutionarily conserved and multiple homologs exist in many species (1). Cullins were first identified in C. elegans, and CUL-1 mutants exhibit tissue hyperplasia resulting from a decreased ability to exit the cell cycle during development, and accelerated G1-to-S phase progression (37). Human CUL1 (OMIM), the closest human CDC53 cullin homolog, is a subunit of a functionally conserved SCF ubiquitin ligase complex that is involved in the degradation of key regulators of the mammalian cell cycle (reviewed in 38). Human CUL1 complements the growth defect of conditional CDC53 mutants and assembles into functional chimeric ubiquitin ligase complexes with yeast components (39).

Last updated: 2007-03-08 Contact SGD

References cited on this page View Complete Literature Guide for CDC53
1) Mathias N, et al.  (1996) Cdc53p acts in concert with Cdc4p and Cdc34p to control the G1-to-S-phase transition and identifies a conserved family of proteins. Mol Cell Biol 16(12):6634-43
2) Feldman RM, et al.  (1997) A complex of Cdc4p, Skp1p, and Cdc53p/cullin catalyzes ubiquitination of the phosphorylated CDK inhibitor Sic1p. Cell 91(2):221-30
3) Seol JH, et al.  (1999) Cdc53/cullin and the essential Hrt1 RING-H2 subunit of SCF define a ubiquitin ligase module that activates the E2 enzyme Cdc34. Genes Dev 13(12):1614-26
4) Willems AR, et al.  (1996) Cdc53 targets phosphorylated G1 cyclins for degradation by the ubiquitin proteolytic pathway. Cell 86(3):453-63
5) Patton EE, et al.  (1998) Cdc53 is a scaffold protein for multiple Cdc34/Skp1/F-box proteincomplexes that regulate cell division and methionine biosynthesis in yeast. Genes Dev 12(5):692-705
6) Hershko A  (1997) Roles of ubiquitin-mediated proteolysis in cell cycle control. Curr Opin Cell Biol 9(6):788-99
7) Craig KL and Tyers M  (1999) The F-box: a new motif for ubiquitin dependent proteolysis in cell cycle regulation and signal transduction. Prog Biophys Mol Biol 72(3):299-328
8) Kamura T, et al.  (2002) Roles of SCF and VHL ubiquitin ligases in regulation of cell growth. Prog Mol Subcell Biol 29:1-15
9) Jackson PK  (1996) Cell cycle: cull and destroy. Curr Biol 6(10):1209-12
10) Bai C, et al.  (1996) SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box. Cell 86(2):263-74
11) Skowyra D, et al.  (1997) F-box proteins are receptors that recruit phosphorylated substrates to the SCF ubiquitin-ligase complex. Cell 91(2):209-19
12) Ohta T, et al.  (1999) ROC1, a homolog of APC11, represents a family of cullin partners with an associated ubiquitin ligase activity. Mol Cell 3(4):535-41
13) Goebl MG, et al.  (1988) The yeast cell cycle gene CDC34 encodes a ubiquitin-conjugating enzyme. Science 241(4871):1331-5
14) Patton EE, et al.  (1998) Combinatorial control in ubiquitin-dependent proteolysis: don't Skp the F-box hypothesis. Trends Genet 14(6):236-43
15) Willems AR, et al.  (1999) SCF ubiquitin protein ligases and phosphorylation-dependent proteolysis. Philos Trans R Soc Lond B Biol Sci 354(1389):1533-50
16) Henchoz S, et al.  (1997) Phosphorylation- and ubiquitin-dependent degradation of the cyclin-dependent kinase inhibitor Far1p in budding yeast. Genes Dev 11(22):3046-60
17) Blondel M, et al.  (2000) Nuclear-specific degradation of Far1 is controlled by the localization of the F-box protein Cdc4. EMBO J 19(22):6085-97
18) Drury LS, et al.  (1997) The Cdc4/34/53 pathway targets Cdc6p for proteolysis in budding yeast. EMBO J 16(19):5966-76
19) Sanchez M, et al.  (1999) The Cdc6 protein is ubiquitinated in vivo for proteolysis in Saccharomyces cerevisiae. J Biol Chem 274(13):9092-7
20) Jackson LP, et al.  (2006) Distinct mechanisms control the stability of the related S-phase cyclins Clb5 and Clb6. Mol Cell Biol 26(6):2456-66
21) Pal B, et al.  (2007) SCFCdc4-mediated degradation of the Hac1p transcription factor regulates the unfolded protein response in Saccharomyces cerevisiae. Mol Biol Cell 18(2):426-40
22) Barral Y, et al.  (1995) G1 cyclin turnover and nutrient uptake are controlled by a common pathway in yeast. Genes Dev 9(4):399-409
23) Jaquenoud M, et al.  (1998) The Cdc42p effector Gic2p is targeted for ubiquitin-dependent degradation by the SCFGrr1 complex. EMBO J 17(18):5360-73
24) Rouillon A, et al.  (2000) Feedback-regulated degradation of the transcriptional activator Met4 is triggered by the SCF(Met30 )complex. EMBO J 19(2):282-94
25) Kaiser P, et al.  (1998) Cdc34 and the F-box protein Met30 are required for degradation of the Cdk-inhibitory kinase Swe1. Genes Dev 12(16):2587-97
26) Bao MZ, et al.  (2004) Pheromone-dependent destruction of the Tec1 transcription factor is required for MAP kinase signaling specificity in yeast. Cell 119(7):991-1000
27) Escusa S, et al.  (2006) Proteasome- and SCF-dependent degradation of yeast adenine deaminase upon transition from proliferation to quiescence requires a new F-box protein named Saf1p. Mol Microbiol 60(4):1014-25
28) Galan JM and Peter M  (1999) Ubiquitin-dependent degradation of multiple F-box proteins by an autocatalytic mechanism. Proc Natl Acad Sci U S A 96(16):9124-9
29) Zhou P and Howley PM  (1998) Ubiquitination and degradation of the substrate recognition subunits of SCF ubiquitin-protein ligases. Mol Cell 2(5):571-80
30) Skowyra D, et al.  (1999) Reconstitution of G1 cyclin ubiquitination with complexes containing SCFGrr1 and Rbx1. Science 284(5414):662-5
31) Schwob E, et al.  (1994) The B-type cyclin kinase inhibitor p40SIC1 controls the G1 to S transition in S. cerevisiae. Cell 79(2):233-44
32) Deshaies RJ, et al.  (1995) Ubiquitination of the G1 cyclin Cln2p by a Cdc34p-dependent pathway. EMBO J 14(2):303-12
33) Chiba T and Tanaka K  (2004) Cullin-based ubiquitin ligase and its control by NEDD8-conjugating system. Curr Protein Pept Sci 5(3):177-84
34) Lammer D, et al.  (1998) Modification of yeast Cdc53p by the ubiquitin-related protein rub1p affects function of the SCFCdc4 complex. Genes Dev 12(7):914-26
35) Liakopoulos D, et al.  (1998) A novel protein modification pathway related to the ubiquitin system. EMBO J 17(8):2208-14
36) Cope GA, et al.  (2002) Role of predicted metalloprotease motif of Jab1/Csn5 in cleavage of Nedd8 from Cul1. Science 298(5593):608-11
37) Kipreos ET, et al.  (1996) cul-1 is required for cell cycle exit in C. elegans and identifies a novel gene family. Cell 85(6):829-39
38) Nakayama KI and Nakayama K  (2006) Ubiquitin ligases: cell-cycle control and cancer. Nat Rev Cancer 6(5):369-81
39) Lyapina SA, et al.  (1998) Human CUL1 forms an evolutionarily conserved ubiquitin ligase complex (SCF) with SKP1 and an F-box protein. Proc Natl Acad Sci U S A 95(13):7451-6