CDC20 (cell division cycle 20 homolog (S. cerevisiae))

2008-04-01 Susanta Roychoudhury , Taraswi Banerjee , Somsubhra Nath Affiliation

Human Genetics, Genomics Division, Indian Institute of Chemical Biology, Kolkata-700 032, India

Identity

HGNC

CDC20

LOCATION

1p34.2

LOCUSID

991

ALIAS

CDC20A,bA276H19.3,p55CDC

FUSION GENES

Show Gene Fusions

DNA/RNA

Description

Start: 43,597,199 bp from pter
End: 43,601,461 bp from pter
Size: 4,262 bases
Orientation: plus strand
13 exons (Entrez), 15 Exons (Ensembl)

Transcription

1697 bp

Pseudogene

Proteins

The N-terminal amino acids from 1-153 contains most of the functional domains consisting of the Kinetochore binding domain, Mad2 binding domain and the Anaphase promoting complex (APC) activation domain. Amino acids 129-499 contain the WD-repeat region.

Description

Size: 499 amino acids; 54723 Da. Subunit: Interacts with MAD2L1. The phosphorylated form interacts with APC/C. Developmental stage: Synthesis is initiated at G1/S, protein level peaks in M phase and protein is abruptly degraded at M/G1 transition.

Expression

It is expressed in all cells, no tissue specificity.

Localisation

Nucleus

Function

CDC20 is a key player in the Spindle Assembly Checkpoint (SAC). When a cell is dividing mitotically, the Metaphase to Anaphase transition is stringently monitored by SAC. After proper alignment of all the sister chromatids to the spindle fibers during metaphase, the Mitotic Checkpoint Complex detaches from CDC20 and free CDC20 protein activates the Anaphase promoting Complex (APC) Activated APC can then degrade Securin which frees the protease Separase. Free Separase can now degrade the Cohesin molecules binding the two sister chromatids together. Upon degradation of Cohesin, the two sister chromatids are free and can migrate to the two spindle poles, thus, initiating Anaphase.

Homology

The C-terminal half is highly conserved from humans to yeast.

Mutations

Germinal

Somatic

Implicated in

Entity name

Various tumors

Disease

There have been few reports of overexpression of CDC20 in various tumors for eg, greater than 3% of Cdc20 expression was found in bladder cancer, breast cancer, cervical cancer, cholangiocellular carcinoma, AML, CML, colon and rectum carcinoma, esophageal cancer, gastric cancer, gastric cancer (diffuse type), liver cancer, lung cancer (NSCLC), lung cancer (SCLC), osteosarcoma, pancreatic cancer, prostate cancer, renal carcinoma, soft tissue tumor, testicular tumor (Kidoko T, et al., 2007), head and neck cancer (Mondal G, et al., 2007).

Prognosis

Cytogenetics

Hybrid gene

Fusion protein

Oncogenesis

Overexpression of CDC20 has been observed in several tumor tissues.

Bibliography

Pubmed ID	Last Year	Title	Authors
10377410	1999	Cdc20 associates with the kinase aurora2/Aik.	Farruggio DC et al
11726501	2001	Bub3 interaction with Mad2, Mad3 and Cdc20 is mediated by WD40 repeats and does not require intact kinetochores.	Fraschini R et al
9628895	1998	Mammalian p55CDC mediates association of the spindle checkpoint protein Mad2 with the cyclosome/anaphase-promoting complex, and is involved in regulating anaphase onset and late mitotic events.	Kallio M et al
17873905	2008	CDC20, a potential cancer therapeutic target, is negatively regulated by p53.	Kidokoro T et al
16497171	2006	A new Mad2-interacting domain of Cdc20 is critical for the function of Mad2-Cdc20 complex in the spindle assembly checkpoint.	Mondal G et al
16777988	2007	Overexpression of Cdc20 leads to impairment of the spindle assembly checkpoint and aneuploidization in oral cancer.	Mondal G et al
12360190	2002	The spindle checkpoint: structural insights into dynamic signalling.	Musacchio A et al
11707408	2001	Mad2 binding to Mad1 and Cdc20, rather than oligomerization, is required for the spindle checkpoint.	Sironi L et al
15525512	2004	Phosphorylation of Cdc20 by Bub1 provides a catalytic mechanism for APC/C inhibition by the spindle checkpoint.	Tang Z et al
9353311	1997	Cell cycle-regulated expression, phosphorylation, and degradation of p55Cdc. A mammalian homolog of CDC20/Fizzy/slp1.	Weinstein J et al
11030144	2000	p55CDC/hCDC20 is associated with BUBR1 and may be a downstream target of the spindle checkpoint kinase.	Wu H et al
17612486	2007	Cdc20: a WD40 activator for a cell cycle degradation machine.	Yu H et al

Other Information

Locus ID:

NCBI: 991
MIM: 603618
HGNC: 1723
Ensembl: ENSG00000117399

Variants:

dbSNP: 991
ClinVar: 991
TCGA: ENSG00000117399
COSMIC: CDC20

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000117399	ENST00000310955	Q12834
ENSG00000117399	ENST00000372462	Q12834

Expression (GTEx)

100

150

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Cell cycle	KEGG	ko04110
Ubiquitin mediated proteolysis	KEGG	ko04120
Cell cycle	KEGG	hsa04110
Ubiquitin mediated proteolysis	KEGG	hsa04120
Oocyte meiosis	KEGG	ko04114
Oocyte meiosis	KEGG	hsa04114
HTLV-I infection	KEGG	ko05166
HTLV-I infection	KEGG	hsa05166
APC/C complex	KEGG	hsa_M00389
APC/C complex	KEGG	M00389
Viral carcinogenesis	KEGG	hsa05203
Viral carcinogenesis	KEGG	ko05203
Metabolism of proteins	REACTOME	R-HSA-392499
Post-translational protein modification	REACTOME	R-HSA-597592
Immune System	REACTOME	R-HSA-168256
Adaptive Immune System	REACTOME	R-HSA-1280218
Class I MHC mediated antigen processing & presentation	REACTOME	R-HSA-983169
Antigen processing: Ubiquitination & Proteasome degradation	REACTOME	R-HSA-983168
Signal Transduction	REACTOME	R-HSA-162582
Signaling by Rho GTPases	REACTOME	R-HSA-194315
RHO GTPase Effectors	REACTOME	R-HSA-195258
RHO GTPases Activate Formins	REACTOME	R-HSA-5663220
Cell Cycle	REACTOME	R-HSA-1640170
Cell Cycle Checkpoints	REACTOME	R-HSA-69620
Mitotic Spindle Checkpoint	REACTOME	R-HSA-69618
Inhibition of the proteolytic activity of APC/C required for the onset of anaphase by mitotic spindle checkpoint components	REACTOME	R-HSA-141405
Inactivation of APC/C via direct inhibition of the APC/C complex	REACTOME	R-HSA-141430
Cell Cycle, Mitotic	REACTOME	R-HSA-69278
M Phase	REACTOME	R-HSA-68886
Mitotic Prometaphase	REACTOME	R-HSA-68877
Resolution of Sister Chromatid Cohesion	REACTOME	R-HSA-2500257
Mitotic Metaphase and Anaphase	REACTOME	R-HSA-2555396
Mitotic Anaphase	REACTOME	R-HSA-68882
Separation of Sister Chromatids	REACTOME	R-HSA-2467813
Regulation of mitotic cell cycle	REACTOME	R-HSA-453276
APC/C-mediated degradation of cell cycle proteins	REACTOME	R-HSA-174143
Regulation of APC/C activators between G1/S and early anaphase	REACTOME	R-HSA-176408
Phosphorylation of Emi1	REACTOME	R-HSA-176417
SCF-beta-TrCP mediated degradation of Emi1	REACTOME	R-HSA-174113
Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins	REACTOME	R-HSA-176814
APC/C:Cdc20 mediated degradation of mitotic proteins	REACTOME	R-HSA-176409
APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint	REACTOME	R-HSA-179419
Cdc20:Phospho-APC/C mediated degradation of Cyclin A	REACTOME	R-HSA-174184
APC-Cdc20 mediated degradation of Nek2A	REACTOME	R-HSA-179409
APC/C:Cdc20 mediated degradation of Cyclin B	REACTOME	R-HSA-174048
APC/C:Cdc20 mediated degradation of Securin	REACTOME	R-HSA-174154
Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase	REACTOME	R-HSA-176407
APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1	REACTOME	R-HSA-174178
Deubiquitination	REACTOME	R-HSA-5688426
Ub-specific processing proteases	REACTOME	R-HSA-5689880

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
18997788	2008	The APC/C maintains the spindle assembly checkpoint by targeting Cdc20 for destruction.	144
20526282	2010	Phosphorylation of Mcl-1 by CDK1-cyclin B1 initiates its Cdc20-dependent destruction during mitotic arrest.	143
19154722	2009	Unattached kinetochores catalyze production of an anaphase inhibitor that requires a Mad2 template to prime Cdc20 for BubR1 binding.	128
20624902	2010	Mps1 directs the assembly of Cdc20 inhibitory complexes during interphase and mitosis to control M phase timing and spindle checkpoint signaling.	95
18471975	2008	Cdc20 and Cks direct the spindle checkpoint-independent destruction of cyclin A.	92
14743218	2004	The tumour suppressor RASSF1A regulates mitosis by inhibiting the APC-Cdc20 complex.	89
17873905	2008	CDC20, a potential cancer therapeutic target, is negatively regulated by p53.	79
25383541	2015	The mitotic checkpoint complex binds a second CDC20 to inhibit active APC/C.	76
22100920	2011	p31comet-mediated extraction of Mad2 from the MCC promotes efficient mitotic exit.	70
15701830	2005	Identification of gastric cancer-related genes using a cDNA microarray containing novel expressed sequence tags expressed in gastric cancer cells.	64

Citation

Susanta Roychoudhury ; Taraswi Banerjee ; Somsubhra Nath

CDC20 (cell division cycle 20 homolog (S. cerevisiae))

Atlas Genet Cytogenet Oncol Haematol. 2008-04-01

Online version: http://atlasgeneticsoncology.org/gene/40003/cdc20