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PDCD10 (Programmed cell death 10)

Written2016-08Urfali-Mamatoglu, Hasan Huseyin Kazan, Ufuk Gunduz
Department of Biological Sciences, Middle East Technical University, Ankara, Turkey. cagri.urfali@metu.edu.tr; hasanhuseyinkazan@gmail.com; ufukg@metu.edu.tr

Abstract PDCD10 is a novel apoptosis regulator which functions in the regulation of cellular proliferation and apoptosis.

Keywords PDCD10, programmed cell death, apoptosis, cell survival, cellular proliferation

(Note : for Links provided by Atlas : click)

Identity

Other aliasCCM3 (Cerebral cavernous malformations 3)
TFAR15 (TF-1 cell apoptosis-related protein 15)
LocusID (NCBI) 11235
Atlas_Id 43399
Location 3q26.1  [Link to chromosome band 3q26]
Location_base_pair Starts at and ends at bp from pter
Local_order From telomere to centromere: LINC01330, MEMO1P3, SERPINI1, PDCD10, HMGN1P8, WDR49, LOC105374197, SERPINI2
 
  Local order of PDCD10 is shown together with leading and subsequent genes on chromosome 3. The direction of arrows indicates transcriptional directions on the chromosome and arrow sizes approximate gene sizes.
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)

DNA/RNA

 
  Boxes are exons and the lines are introns.
Description The PDCD10 gene is 51,688 bp in length, located on the minus strand and spans 9 exons (NCBI, 2016).
Transcription 3 different alternatively spliced mRNAs (1454, 1313 and 1212 bp long, respectively) that differ only in 5'UTRs; 639 bp long open reading frame (NM_007217.3, NM_145859.1, NM_145860.1).
Pseudogene LOC100128686 programmed cell death 10 pseudogene; located on 8q11.21 (NCBI, 2016).

Protein

Description PDCD10 encodes an evolutionarily conserved 212 amino acid long protein (Wang et al, 1999). PDCD10 has an estimated molecular weight of 29 kDa.
Expression PDCD10 is expressed in all tissues including brain, pancreas, breast, ovary, kidney, liver and lungs (The Human Protein Atlas, 2016).
Localisation PDCD10 is localized in cytoplasm, near Golgi apparatus and nucleus (Fidalgo et al, 2010).
Function The PDCD10 protein regulates cell proliferation and transformation by modulating the extracellular signal-regulated kinase (ERK) pathway through interaction with serine/threonine protein kinase STK26 (MST4) (Ma et al, 2007). It also interacts with another serine/threonine kinase, STK25 , and triggers apoptosis under oxidative stress (Zhang et al, 2012). PDCD10 interacts with members of germinal center kinases III subfamily to promote normal Golgi assembly and cell orientation (Fidalgo, 2010). PDCD10 involves in the stabilization of KDR (VEGFR2) signaling and is vital for normal vascular development (He et al, 2010). PDCD10 acts downstream of gamma-protocadherins and regulate neuronal survival (Lin et al, 2010).

Mutations

Germinal Cerebral cavernous malformations are associated with the mutations in 3 loci; one of which is CCM3/PDCD10. Bergametti et al reported a de novo deletion as well as six other deleterious mutations in PDCD10 gene. Three of these mutations were stated as nonsense mutations, two other mutations were reported to generate aberrant splicing in exon 9 with a frameshift and the last one caused an abnormal splicing in exon 5 without frameshift (Bergametti et al, 2005). In a study with 61 families with cerebral caverous malformations, Guclu et al (2005) identified two identical mutations creating a premature stop codon in exon 7, two frameshift mutations in exon 6 and one additional frameshift mutation in exon 9 (Guclu et al, 2005). In patients without KRIT1 (CCM1) and CCM2 mutations, Verlaan et al (2005) identified two mutations in CCM3 which lead to a truncated PDCD10 protein. One of the mutations was a nonsense mutation in exon 7 caused by a transversion o a C to a T that creates a stop codon and the other one was reported to be an invariant splice acceptor site mutation (Verlaan et al, 2005). Riant et al (2013) reported that, in 13 of 54 CCM3-mutated patients, there are deletions in one or several coding exons; 8 of which deletions are whole gene deletions. In 41 patients, several point mutations leading abnormal splicing, nonsense mutations and small insertions and deletions causing frameshifts and premature stop codons were identified. Additionally, they reported deletions in noncoding exons 1-3 in a 5-year old child with cerebral carcinomas (Riant et al, 3013).

Implicated in

  
Entity Cerebral cavernous malformations
Disease Cerebral cavernous malformations (CCM) is one of the frequently occurring cerebral vascular abnormalities characterized by abnormally enlarged blood vessels that cause brain hemorrhages and seizures which result in focal neurological deficits (Rigamonti et al, 1998; Bergametti et al, 2005). Bergametti et al identified PDCD10 as the CCM3 gene and reported several mutations in this locus (Bergametti et al, 2005). Several other studies also reported different mutations in PDCD10 gene in patients with cerebral cavernous malformations and cerebral carcinomas (see Mutations section above).
  
  
Entity Prostate cancer
Note PDCD10 is expressed in both benign prostatic hyperplasia and prostate cancer with a stronger staining in prostate cancer cases. Germinal center kinases, MST4 and STK25, are also significantly overexpressed in prostate cancer and associated with the PDCD10 expression (Zhang et al, 2014). miR-103 is reported to regulate PDCD10 in prostate cancer and when overexpressed, it suppresses tumor cell proliferation by targeting PDCD10 (Fu et al, 2016).
  
  
Entity T cell lymphoma
Note PDCD10 is constitutiely expressed in malignant T cells and cell lines derived from peripheral blood of patients with Sezary syndrome (T cell lymphoma). PDCD10 is found to be constitutively associated with protein phosphatase-2A (PP2A) which is essential in the regulation of cell proliferation and apoptosis in T cell lymphoma. Depletion of PDCD10 was reported to significantly increase apoptosis in various malignant T cells (Lauenborg et al, 2010).
  
  
Entity Colorectal cancer
Note Zhang et al (2016) reported that PDCD10 expression was down-regulated in drug-resistant colorectal cancer cells. The expression of PDCD10 was regulated by MIR425 (mature sequence miR-425-5p) which directly targets 3'-UTR of PDCD10 (Zhang et al, 2016).
  

Bibliography

Mutations within the programmed cell death 10 gene cause cerebral cavernous malformations
Bergametti F, Denier C, Labauge P, Arnoult M, Boetto S, Clanet M, Coubes P, Echenne B, Ibrahim R, Irthum B, Jacquet G, Lonjon M, Moreau JJ, Neau JP, Parker F, Tremoulet M, Tournier-Lasserve E; Société Française de Neurochirurgie
Am J Hum Genet 2005 Jan;76(1):42-51
PMID 15543491
 
CCM3/PDCD10 stabilizes GCKIII proteins to promote Golgi assembly and cell orientation
Fidalgo M, Fraile M, Pires A, Force T, Pombo C, Zalvide J
J Cell Sci 2010 Apr 15;123(Pt 8):1274-84
PMID 20332113
 
MicroRNA-103 suppresses tumor cell proliferation by targeting PDCD10 in prostate cancer
Fu X, Zhang W, Su Y, Lu L, Wang D, Wang H
Prostate 2016 May;76(6):543-51
PMID 26771762
 
Mutations in apoptosis-related gene, PDCD10, cause cerebral cavernous malformation 3
Guclu B, Ozturk AK, Pricola KL, Bilguvar K, Shin D, O'Roak BJ, Gunel M
Neurosurgery 2005 Nov;57(5):1008-13
PMID 16284570
 
Stabilization of VEGFR2 signaling by cerebral cavernous malformation 3 is critical for vascular development
He Y, Zhang H, Yu L, Gunel M, Boggon TJ, Chen H, Min W
Sci Signal 2010 Apr 6;3(116):ra26
PMID 20371769
 
Programmed cell death-10 enhances proliferation and protects malignant T cells from apoptosis
Lauenborg B, Kopp K, Krejsgaard T, Eriksen KW, Geisler C, Dabelsteen S, Gniadecki R, Zhang Q, Wasik MA, Woetmann A, Odum N
APMIS 2010 Oct;118(10):719-28
PMID 20854465
 
PDCD10/CCM3 acts downstream of {gamma}-protocadherins to regulate neuronal survival
Lin C, Meng S, Zhu T, Wang X
J Biol Chem 2010 Dec 31;285(53):41675-85
 
PDCD10 interacts with Ste20-related kinase MST4 to promote cell growth and transformation via modulation of the ERK pathway
Ma X, Zhao H, Shan J, Long F, Chen Y, Chen Y, Zhang Y, Han X, Ma D
Mol Biol Cell 2007 Jun;18(6):1965-78
PMID 17360971
 
CCM3 Mutations Are Associated with Early-Onset Cerebral Hemorrhage and Multiple Meningiomas
Riant F, Bergametti F, Fournier HD, Chapon F, Michalak-Provost S, Cecillon M, Lejeune P, Hosseini H, Choe C, Orth M, Bernreuther C, Boulday G, Denier C, Labauge P, Tournier-Lasserve E
Mol Syndromol 2013 Apr;4(4):165-72
PMID 23801932
 
CCM3 mutations are uncommon in cerebral cavernous malformations
Verlaan DJ, Roussel J, Laurent SB, Elger CE, Siegel AM, Rouleau GA
Neurology 2005 Dec 27;65(12):1982-3
PMID 16380626
 
cDNA cloning and expression of an apoptosis-related gene, humanTFAR15 gene
Wang Y, Liu H, Zhang Y, Ma D
Sci China C Life Sci 1999 Jun;42(3):323-9
PMID 20229348
 
PDCD10 interacts with STK25 to accelerate cell apoptosis under oxidative stress
Zhang H, Ma X, Deng X, Chen Y, Mo X, Zhang Y, Zhao H, Ma D
Front Biosci (Landmark Ed) 2012 Jun 1;17:2295-305
PMID 22652780
 

Citation

This paper should be referenced as such :
Urfali-Mamatoglu Hasan, Huseyin Kazan, Ufuk Gunduz
PDCD10 (Programmed cell death 10)
Atlas Genet Cytogenet Oncol Haematol. 2017;21(3):95-97.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/PDCD10ID43399ch3q26.html


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 1 ]
  GPR160/PDCD10 (3q26)


External links

Nomenclature
Cards
AtlasPDCD10ID43399ch3q26.txt
Aliases
Genomic and cartography
Gene and transcription
RefSeq transcript (Entrez)
RefSeq genomic (Entrez)
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
BioGPS (Tissue expression)11235
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Protein Interaction databases
Ontologies - Pathways
Clinical trials, drugs, therapy
Miscellaneous
canSAR (ICR) (select the gene name)
Other databasePDCD10 Protein Atlas
Other databasePDCD10 NBCI
Probes
Litterature
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed


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indexed on : Thu Oct 18 17:46:56 CEST 2018

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