YPEL3 (yippee-like 3 (Drosophila))

2014-04-01 Gizem Güpür , Mesut Muyan Affiliation

Department of Biological Sciences, Middle East Technical University, Ankara, Turkey

Identity

HGNC

YPEL3

LOCATION

16p11.2

IMAGE

LEGEND

Local order of YPEL3 is shown together with leading and subsequent genes on chromosome 16.

LOCUSID

83719

ALIAS

FUSION GENES

Show Gene Fusions

DNA/RNA

Boxes show exons; filled boxes correspond to coding exons, empty boxes indicate noncoding exons. Lines connecting the boxes represent introns. Arrows indicate the translation initiation codon.

Description

YPEL3 has 4 exons.

Transcription

YPEL3 has 2 transcript variants, resulting from the differential processing of the exon 1.
Transcript variant 1: 1588 bp mRNA (NCBI RefSeq NM_031477.4).
Transcript variant 2: 940 bp mRNA (NCBI RefSeq NM_001145524.1).

Proteins

Note

Two transcript variants encode two protein isoforms differing at their amino-termini.
Protein yippee-like 3 isoform 1; 157 aa protein (NCBI RefSeq NP_113665.3).
Protein yippee-like 3 isoform 2; 119 aa protein (NCBI RefSeq NP_001138996.1).

Expression

In human, YPEL3 is expressed in the brain, heart, kidney, lung, pancreas, placenta, skeletal muscle, colon, ovary, leukocyte, prostate, small intestine, spleen, testis, thymus, bone marrow, leukocyte, tonsil, fetal brain, fetal heart, fetal kidney, fetal liver, fetal lung, fetal skeletal muscle, fetal spleen and fetal thymus (Hosono et al., 2004).

Localisation

Immunofluorescence staining with an antibody recognizing Ypel1, 2, 3 and 4 proteins suggests that Ypel1-4 are nuclear proteins. In interphase cells, Ypel1-4 are localized in nucleoli and the centrosome. In the mitotic phase, Ypel1-4 become localized on or close to the mitotic apparatus rather than in the centrosome (Hosono et al., 2004).

Function

Studies show that the expression of YPEL3 gene is up-regulated during DNA damage, reflected as an increase in YPEL protein levels, likely through two functional p53 binding sites present on the YPEL3 gene promoter (Kelley et al., 2010).
When YPEL3 is expressed by a tetracycline inducible system at levels comparable to endogenous mRNA levels detected upon DNA damage, both MCF7 and U2OS cells showed fewer colonies compared to uninduced cells. YPEL3 expressing U2OS and MCF7 cells also showed an increase in cellular senescence as shown by increases β-galactosidase activity and the appearance of foci within the nuclei of senescent cells (SAHF) (Kelley et al., 2010).

Homology

In human, YPEL3 has 4 paralogs; YPEL1, YPEL2, YPEL4 and YPEL5. Ypel3 has 88.2% aminoacid sequence identity with Ypel1; 89.1% with Ypel2; 83.9% with Ypel4 and 43.8% with Ypel5 (Hosono et al., 2004).
Ypel3 is an ortholog of Drosophila Yippee protein and has 45.5% aminoacid sequence identity to Yippee. There are 100 YPEL family genes in 68 species including mammal, bird, amphibia, fish, protochordate, insect, nematode, coelenterate, echinoderm, protozoan, plant, and fungi. In this diverge range of organisms, YPEL family proteins show a high level of homology with many identical residues. Thus, a consensus sequence is deduced as follows: C-X2-C-X19-G-X3-L-X5-N-X13-G-X8-C-X2-C-X4-GWXY-X10-K-X6-E. In the consensus sequence, the number of non-consensus residues, designated as X, is identical for all species examined (Hosono et al., 2004).

Implicated in

Entity name

Colon cancer

Note

YPEL3 is found to be down-regulated in 9 commercial colon tumor samples and in 22 patient colon adenocarcinoma (Tuttle et al., 2011).

Entity name

Ovarian cancer

Note

A significant decrease in YPEL3 mRNA levels was detected in 9 commercial and 30 patient ovarian tumors. In Cp70 ovarian cells, hypermethylation of a CpG island immediately upstream of the YPEL3 promoter is suggested to be the basis for the observed down-regulation (Kelley et al., 2010).

Entity name

Lung cancer

Note

YPEL3 mRNA is shown to be down-regulated in 8 of 9 commercial lung tumor samples (Tuttle et al., 2011).

Entity name

Breast cancer

Note

YPEL3 is observed to be down-regulated in breast cancer cell models. Decrease in YPEL3 mRNA levels by siRNA causes an increase in the growth of estrogen receptor positive (ER+) MCF7 cells while YPEL3 over-expression decreases cell number. Moreover, YPEL3 mRNA as well as Ypel protein levels show an increase in MCF7 cells when 17β-estradiol (E2) is withdrawn. In contrast, the addition of E2 at a circulating level (1nM) decreases the expression of YPEL3. The down-regulation of YPEL3 by E2 can be reversed by the addition of selective estrogen receptor modulator, tamoxifen, TMX (Tuttle et al., 2012).
In addition to p53, E2-ER signaling plays a role in the regulation of YPEL3 gene expression based on the observations that the reduction of intracellular ERa levels in MCF7 cells by ERa knockdown increases the expression of YPEL3 gene (Tuttle et al., 2012).
Studies also showed that when grown in the absence of E2, MCF7 cells undergo cellular senescence, whereas the silencing of YPEL3 rescues cells from senescence. Further evidence that YPEL3 is involved in E2-ER mediated cellular senescence was obtained from studies showing that the treatment of MCF7 cells with TMX increases the expression of the YPEL3 gene and that TMX-induced cellular senescence is not observed when YPEL3 is silenced. Importantly, cellular senescence induced by removal of E2 and/or over-expression of YPEL3 is independent of p53 expression. Thus, it appears that YPEL3 plays a role in E2-ER signaling dependent cellular growth and senescence in MCF7 cells. This in turn implies that Ypel3 is a tumor suppressor protein (Tuttle et al., 2012).

Bibliography

Pubmed ID	Last Year	Title	Authors
15556292	2004	Identification and characterization of a novel gene family YPEL in a wide spectrum of eukaryotic species.	Hosono K et al
20388804	2010	YPEL3, a p53-regulated gene that induces cellular senescence.	Kelley KD et al
21671470	2012	Novel senescence associated gene, YPEL3, is repressed by estrogen in ER+ mammary tumor cells and required for tamoxifen-induced cellular senescence.	Tuttle R et al
21267786	2011	Senescence-associated gene YPEL3 is downregulated in human colon tumors.	Tuttle R et al

Other Information

Locus ID:

NCBI: 83719
MIM: 609724
HGNC: 18327
Ensembl: ENSG00000090238

Variants:

dbSNP: 83719
ClinVar: 83719
TCGA: ENSG00000090238
COSMIC: YPEL3

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000090238	ENST00000398838	P61236
ENSG00000090238	ENST00000398838	A0A024R624
ENSG00000090238	ENST00000398841	P61236
ENSG00000090238	ENST00000562641	A0A0B4J290
ENSG00000090238	ENST00000563788	P61236
ENSG00000090238	ENST00000563788	A0A024R624
ENSG00000090238	ENST00000565110	H3BME7
ENSG00000090238	ENST00000566134	H3BUE2
ENSG00000090238	ENST00000566401	H3BRF0
ENSG00000090238	ENST00000566595	P61236
ENSG00000090238	ENST00000566595	A0A024R624
ENSG00000090238	ENST00000570099	H3BNP5

Expression (GTEx)

100

150

200

250

300

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

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
20388804	2010	YPEL3, a p53-regulated gene that induces cellular senescence.	17
20508983	2011	Centrosome-related genes, genetic variation, and risk of breast cancer.	16
27400785	2016	YPEL3 suppresses epithelial-mesenchymal transition and metastasis of nasopharyngeal carcinoma cells through the Wnt/β-catenin signaling pathway.	14
21671470	2012	Novel senescence associated gene, YPEL3, is repressed by estrogen in ER+ mammary tumor cells and required for tamoxifen-induced cellular senescence.	11
21196260	2011	Why YPEL3 represents a novel tumor suppressor.	3
21267786	2011	Senescence-associated gene YPEL3 is downregulated in human colon tumors.	3
29988027	2018	Increased Expression of the YPEL3 Gene in Human Colonic Adenocarcinoma Tissue and the Effects on Proliferation, Migration, and Invasion of Colonic Adenocarcinoma Cells In Vitro via the Wnt/b-Catenin Signaling Pathway.	0

Citation

Gizem Güpür ; Mesut Muyan

YPEL3 (yippee-like 3 (Drosophila))

Atlas Genet Cytogenet Oncol Haematol. 2014-04-01

Online version: http://atlasgeneticsoncology.org/gene/51528/ypel3