PDCD5 (programmed cell death 5)

2014-10-01 Yingyu Chen , Ge Li Affiliation

Key Laboratory of Medical Immunology, Ministry of Health, Peking University Health Science Center, Beijing, 100191, China

Identity

HGNC

PDCD5

LOCATION

19q13.11

LOCUSID

9141

ALIAS

TFAR19

FUSION GENES

Show Gene Fusions

Abstract

Programmed Cell Death 5 (PDCD5) was originally identified as an apoptosis-accelerating molecule that was widely expressed and well-conserved in the process of evolution. It has significant homology to the corresponding proteins of species ranging from yeast to mice gene. PDCD5 can accelerate apoptosis in different type of cells in response to different stimuli, and can also induce different types of cell death, including paraptosis-like cell death. In cells undergoing apoptosis, PDCD5 rapidly translocates from the cytoplasm to the nucleus before phosphatidylserine is externalized and genomic DNA undergoes fragmentation. PDCD5 interacts with TIP60 and TP53 and plays an important positive role in TIP60-P53 signaling pathway. PDCD5 also participates in immune regulation through regulating the level of FOXP3 protein and percentage of regulatory T cells. Dysfunction of PDCD5 was associated in many diseases including different tumors, rheumatoid arthritis and presbycusis, etc.

DNA/RNA

The DNA sequence of PDCD5.

Description

The PDCD5 gene, with 6286 bases in length, consists of 6 exons and 5 intervening introns.

Transcription

The PDCD5 gene encodes a 604 bp mRNA transcript. Transcription site is located 75 bp upstream the first ATG of the PDCD5 ORF. The translation start site is located in exon 1.

Pseudogene

Pseudogenes have been identified on chromosomes 12p12.3 and 5q13.2.

Proteins

Description

PDCD5 protein is composed of 125 amino acids, with a calculated molecular mass of 14.285 kDa. In the protein sequence exist six phosphorylation sites, including a cAMP and cGMP depended protein kinase phosphorylation site (Ser100), 4 PKC phosphorylation sites (Ser51, Ser84, Thr103, Thr108), and a casein kinase 2 (CK2) phosphorylation site (Ser118) (Saivi et al., 2009). Five of the phosphorylation sites are located in the C-terminal region.

Expression

PDCD5 is widely expressed in different organs and different stages. Decreased expression of PDCD5 has been detected in various human tumors, such as lung cancer, gastric cancer, chronic myelogenous leukemia, prostate cancer, chondrosarcoma and epithelial ovarian carcinomas. The abnormal expression of PDCD5 is also involved in some autoimmune diseases and inflammatory processes, such as lupus nephritis, osteoarthritis, rheumatoid arthritis, hepatitis, sepsis and bronchial asthma. In the patients with rheumatoid arthritis, the levels of PDCD5 in serum and synovial fluid are inversely associated with the expression of inflammatory cytokines IL-17 and TNF- α and disease activity.

Localisation

PDCD5 protein has been reported to be localized mainly in the cytoplasm and nucleus, and translocated to the nucleus during apoptosis (Chen et al., 2006).

Function

PDCD5 can promote apoptosis in different cell types in response to various stimuli. PDCD5 interacts with the histone acetyltransferase TIP60 and the transcription factor TP53 to promote apoptosis (Xu et al., 2009; Xu et al., 2012). PDCD5 can also interact with other molecules such as NF-kB p65 and CCT in which participate in the regulation of cell apoptosis. It also associates with TAJ/TROY-induced paraptosis-like cell death (Wang et al., 2004), focal cerebral ischemic reperfusion injury (Jiang et al., 2014), virus infections (Li et al., 2014) and cardiac remodeling (An et al., 2012). PDCD5 negatively regulates autoimmunity by enhancing the level of FOXP3 protein, upregulating FOXP3+ regulatory T cells and suppressing Th17 and Th1 responses (Xiao et al., 2013).

Homology

PDCD5 gene is highly-conserved among species (from yeast to human).

Mutations

Germinal

No data.

Somatic

The promoter with -27G/-11A is associated with reduced PDCD5 promoter activity and increased susceptibility to chronic myelogenous leukemia (Ma et al., 2005). A C/G polymorphism (rs1862214) located 35 kb upstream of the PDCD5 gene was associated with lung cancer susceptibility (Spinola et al., 2006).

Implicated in

Entity name

Various cancers

Note

Reduced PDCD5 expression has been found in a few types of human tumors and is also associated with the high progression and poor prognosis. Decreased expression of PDCD5 has been reported in various human tumors, such as gastric cancer (Gao et al., 2012), brain tumors (Li et al., 2008), bone tumor (Chen et al., 2010a), ovarian carcinomas (Zhang et al., 2011), leukemia (Ruan et al., 2006), renal tumor (Tan et al., 2006), lung cancer (Spinola et al., 2006), prostate cancer (Du et al., 2009), hepatocellular cancer (Fu et al., 2013), laryngeal cancer (Xu et al., 2013), oral squamous cell carcinoma (Zhao et al., 2013) and cervical cancer (Liu et al., 2013). PDCD5 expression predicts a favorable outcome in patients with hepatocellular carcinoma, epithelial ovarian carcinomas, chondrosarcoma.
PDCD5 may make significance to inhibit tumor malignant transformation and progress. Recombinant human PDCD5 (rhPDCD5) has been shown to enter a variety of cells by clathrin-independent endocytosis and exert biological activities. RhPDCD5 could enhance cell death of tumor cells and enhance the sensitivity to chemotherapeutic, such as cisplatin (Chen et al., 2010b; Shi et al., 2010; Wang et al., 2013c).

Entity name

Rheumatoid arthritis

Note

PDCD5 is associated with rheumatoid arthritis and osteoarthritis, which can regulate the apoptosis of synoviocytes and chondrocytes (Wang et al., 2007). The levels of PDCD5 in serum, synovial fluid and cartilage are higher in RA and OA than healthy control, which are negatively correlated with IL-17 or TNF-α levels (Wang et al., 2013a). The expression of PDCD5 may be down regulated by Insulin-like growth factor 1 (Yi et al., 2013). Recombinant human PDCD5 has an anti-inflammatory effect in collagen-induced arthritis (CIA) rats (Xiao et al., 2014).

Bibliography

Pubmed ID	Last Year	Title	Authors
20349137	2010	Recombinant human PDCD5 sensitizes chondrosarcomas to cisplatin chemotherapy in vitro and in vivo.	Chen C et al
23638963	2013	The involvement of programmed cell death 5 (PDCD5) in the regulation of apoptosis in cerebral ischemia/reperfusion injury.	Chen CH et al
11741587	2001	Nuclear translocation of PDCD5 (TFAR19): an early signal for apoptosis?	Chen Y et al
20120772	2009	Reduced expression of programmed cell death 5 protein in tissue of human prostate cancer.	Du YJ et al
24469044	2015	The von Hippel-Lindau tumor suppressor regulates programmed cell death 5-mediated degradation of Mdm2.	Essers PB et al
23807738	2013	PDCD5 expression predicts a favorable outcome in patients with hepatocellular carcinoma.	Fu DZ et al
22965478	2012	The clinical significance of reduced programmed cell death 5 expression in human gastrointestinal stromal tumors.	Gao F et al
24614334	2014	Autophagic effect of programmed cell death 5 (PDCD5) after focal cerebral ischemic reperfusion injury in rats.	Jiang Z et al
18695908	2008	Reduced expression of PDCD5 is associated with high-grade astrocytic gliomas.	Li H et al
24509810	2014	Pretreatment of mice with oligonucleotide prop5 protects them from influenza virus infections.	Li K et al
9920759	1999	TFAR19, a novel apoptosis-related gene cloned from human leukemia cell line TF-1, could enhance apoptosis of some tumor cells induced by growth factor withdrawal.	Liu H et al
16361542	2005	Two single-nucleotide polymorphisms with linkage disequilibrium in the human programmed cell death 5 gene 5' regulatory region affect promoter activity and the susceptibility of chronic myelogenous leukemia in Chinese population.	Ma X et al
19616514	2009	Programmed cell death protein 5 (PDCD5) is phosphorylated by CK2 in vitro and in 293T cells.	Salvi M et al
20398626	2010	Potent antitumor activities of recombinant human PDCD5 protein in combination with chemotherapy drugs in K562 cells.	Shi L et al
16549820	2006	Association of the PDCD5 locus with lung cancer risk and prognosis in smokers.	Spinola M et al
24375412	2014	Programmed cell death protein 5 interacts with the cytosolic chaperonin containing tailless complex polypeptide 1 (CCT) to regulate β-tubulin folding.	Tracy CM et al
23327497	2013	Plasma and synovial fluid programmed cell death 5 (PDCD5) levels are inversely associated with TNF-α and disease activity in patients with rheumatoid arthritis.	Wang J et al
23324280	2013	Programmed cell death 5 correlates with disease activity and interleukin-17 in serum and synovial fluid of rheumatoid arthritis patients.	Wang JF et al
24219296	2013	Recombinant human PDCD5 protein enhances chemosensitivity of breast cancer in vitro and in vivo.	Wang L et al
17468978	2007	Involvement of PDCD5 in the regulation of apoptosis in fibroblast-like synoviocytes of rheumatoid arthritis.	Wang N et al
15020679	2004	An alternative form of paraptosis-like cell death, triggered by TAJ/TROY and enhanced by PDCD5 overexpression.	Wang Y et al
25178696	2015	Anti-inflammatory effects of recombinant human PDCD5 (rhPDCD5) in a rat collagen-induced model of arthritis.	Xiao J et al
24012345	2013	PDCD5 negatively regulates autoimmunity by upregulating FOXP3(+) regulatory T cells and suppressing Th17 and Th1 responses.	Xiao J et al
24265335	2013	Expression and clinical significance of the programmed cell death 5 gene and protein in laryngeal squamous cell carcinoma.	Xu F et al
19308289	2009	PDCD5 interacts with Tip60 and functions as a cooperator in acetyltransferase activity and DNA damage-induced apoptosis.	Xu L et al
22914926	2012	PDCD5 interacts with p53 and functions as a positive regulator in the p53 pathway.	Xu L et al
25109624	2014	Expression of programmed cell death 5 protein inhibits progression of lung carcinoma in vitro and in vivo via the mitochondrial apoptotic pathway.	Xu S et al
23322062	2013	Down-regulation of programmed cell death 5 by insulin-like growth factor 1 in osteoarthritis chondrocytes.	Yi C et al
21165576	2011	Clinical and prognostic significance of lost or decreased PDCD5 expression in human epithelial ovarian carcinomas.	Zhang X et al

Other Information

Locus ID:

NCBI: 9141
MIM: 604583
HGNC: 8764
Ensembl: ENSG00000105185

Variants:

dbSNP: 9141
ClinVar: 9141
TCGA: ENSG00000105185
COSMIC: PDCD5

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000105185	ENST00000221784	X6R2P6
ENSG00000105185	ENST00000379316	Q3HM38
ENSG00000105185	ENST00000419343	O14737
ENSG00000105185	ENST00000586035	K7EQA1
ENSG00000105185	ENST00000590247	O14737
ENSG00000105185	ENST00000592786	K7ESJ4

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

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
19308289	2009	PDCD5 interacts with Tip60 and functions as a cooperator in acetyltransferase activity and DNA damage-induced apoptosis.	26
19789190	2009	A gene-based risk score for lung cancer susceptibility in smokers and ex-smokers.	23
20453000	2010	A Large-scale genetic association study of esophageal adenocarcinoma risk.	23
23369618	2013	Whole-genome DNA methylation in skin lesions from patients with psoriasis vulgaris.	22
16549820	2006	Association of the PDCD5 locus with lung cancer risk and prognosis in smokers.	21
22914926	2012	PDCD5 interacts with p53 and functions as a positive regulator in the p53 pathway.	20
16547588	2006	Expression of programmed cell death 5 gene involves in regulation of apoptosis in gastric tumor cells.	18
26077467	2015	Programmed cell death 5 mediates HDAC3 decay to promote genotoxic stress response.	16
17468978	2007	Involvement of PDCD5 in the regulation of apoptosis in fibroblast-like synoviocytes of rheumatoid arthritis.	14
24375412	2014	Programmed cell death protein 5 interacts with the cytosolic chaperonin containing tailless complex polypeptide 1 (CCT) to regulate β-tubulin folding.	13

Citation

Yingyu Chen ; Ge Li

PDCD5 (programmed cell death 5)

Atlas Genet Cytogenet Oncol Haematol. 2014-10-01

Online version: http://atlasgeneticsoncology.org/gene/41676/pdcd5