A Novel Tissue and Stem Cell Specific TERF1 Splice Variant Is Downregulated in Tumour Cells.
TERF1
cancer
spermatogoina
stem cells
telomere
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
20 Dec 2019
20 Dec 2019
Historique:
received:
11
11
2019
revised:
16
12
2019
accepted:
17
12
2019
entrez:
28
12
2019
pubmed:
28
12
2019
medline:
16
5
2020
Statut:
epublish
Résumé
In this study, we describe the identification of a novel splice variant of TERF1/PIN2, one of the main components of the telomeric shelterin complex. This new splice variant is identical to TERF1, apart from a 30 amino acid internal insertion near to the C-terminus of TERF1. Based on genome comparison analyses and RNA expression data, we show that this splice variant is conserved among hominidae but absent from all other species. RNA expression and histological analyses show specific expression in human spermatogonial and hematopoietic stem cells (HSCs), while all other analyzed tissues lack the expression of this TERF1-isoform, hence the name TERF1-tsi (TERF1-tissue-specific-isoform). In addition, we could not detect any expression in primary human cells and established cancer cell lines. Immunohistochemistry results involving two new rabbit polyclonal antibodies, generated against TERF1-tsi specific peptides, indicate nuclear localization of TERF1-tsi in a subset of spermatogonial stem cells. In line with this observation, immunofluorescence analyzes in various cell lines consistently revealed that ectopic TERF1-tsi localizes to the cell nucleus, mainly but not exclusively at telomeres. In a first attempt to evaluate the impact of TERF1-tsi in the testis, we have tested its expression in normal testis samples versus matched tumor samples from the same patients. Both RT-PCR and IHC show a specific downregulation of TERF1-tsi in tumor samples while the expression of TERF1 and PIN2 remains unchanged.
Identifiants
pubmed: 31877678
pii: ijms21010085
doi: 10.3390/ijms21010085
pmc: PMC6981981
pii:
doi:
Substances chimiques
Protein Isoforms
0
Shelterin Complex
0
TERF1 protein, human
0
Telomere-Binding Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Références
Nat Commun. 2013;4:1946
pubmed: 23735977
Cancer Med. 2012 Oct;1(2):165-75
pubmed: 23342266
Nature. 1996 Apr 11;380(6574):544-7
pubmed: 8606777
Mol Reprod Dev. 2009 Mar;76(3):309-17
pubmed: 18729084
Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13618-23
pubmed: 9391075
FEBS Lett. 2002 Mar 13;514(2-3):193-8
pubmed: 11943150
Am J Pathol. 2002 Apr;160(4):1259-68
pubmed: 11943711
Oncotarget. 2016 Sep 6;7(36):57811-57820
pubmed: 27506934
Mod Pathol. 2014 Sep;27(9):1255-1266
pubmed: 24457464
Carcinogenesis. 2010 Jan;31(1):9-18
pubmed: 19887512
EMBO J. 2012 Jun 29;31(13):2833-4
pubmed: 22643218
Mol Cell Biol. 1992 Nov;12(11):4834-43
pubmed: 1406665
Nat Struct Mol Biol. 2007 Aug;14(8):754-61
pubmed: 17632522
Oncotarget. 2017 Apr 11;8(15):25442-25454
pubmed: 28424414
Mol Cell Biol. 2010 Feb;30(4):1059-66
pubmed: 19995905
Mol Cell Biol. 2009 Aug;29(16):4519-26
pubmed: 19528237
Nat Cell Biol. 2008 Feb;10(2):228-36
pubmed: 18157120
Exp Cell Res. 2005 May 15;306(1):64-74
pubmed: 15878333
Curr Biol. 1998 May 21;8(11):657-60
pubmed: 9635193
Nature. 1991 Apr 18;350(6319):569-73
pubmed: 1708110
Science. 2012 May 4;336(6081):593-7
pubmed: 22556254
Cell. 2010 Apr 2;141(1):81-93
pubmed: 20371347
Cell Rep. 2013 Jun 27;3(6):2059-74
pubmed: 23791526
Proc Natl Acad Sci U S A. 2001 Oct 23;98(22):12683-8
pubmed: 11675499
Mol Hum Reprod. 2017 Feb 10;23(2):79-90
pubmed: 28093458
Semin Cancer Biol. 2011 Dec;21(6):349-53
pubmed: 22015685
Gastroenterology. 2011 Jul;141(1):326-37, 337.e1-3
pubmed: 21447332
Biomed Res Int. 2017;2017:9764752
pubmed: 28808664
Cancer J Sci Am. 1998 May;4 Suppl 1:S22-5
pubmed: 9619267
Int J Cancer. 2013 May 1;132(9):2032-43
pubmed: 23023397
Clin Genitourin Cancer. 2013 Dec;11(4):489-94
pubmed: 23850550
Cell Cycle. 2014;13(23):3742-9
pubmed: 25483083
Genes Dev. 2005 Sep 15;19(18):2100-10
pubmed: 16166375
Int J Oncol. 2001 Sep;19(3):507-12
pubmed: 11494028
Trends Genet. 1997 Jan;13(1):21-6
pubmed: 9009844
Cell. 2009 Jul 10;138(1):90-103
pubmed: 19596237
Curr Biol. 2001 Oct 2;11(19):1512-6
pubmed: 11591318
Annu Rev Genet. 2008;42:301-34
pubmed: 18680434
Am J Pathol. 2005 Jan;166(1):73-80
pubmed: 15632001
Genes Dev. 2009 Sep 1;23(17):2060-75
pubmed: 19679647
Anticancer Res. 2002 Nov-Dec;22(6A):3303-7
pubmed: 12530079
Int J Mol Sci. 2019 Nov 16;20(22):null
pubmed: 31744138
J Pathol. 2011 Aug;224(4):473-83
pubmed: 21706474
Genes (Basel). 2016 Jul 29;7(8):null
pubmed: 27483324
Nat Rev Cancer. 2003 Aug;3(8):623-7
pubmed: 12894250
Nat Chem Biol. 2007 Oct;3(10):640-9
pubmed: 17876321
Nat Rev Urol. 2018 Jun;15(6):386-393
pubmed: 29599449
Cell. 1998 Feb 6;92(3):401-13
pubmed: 9476899
Exp Hematol. 2011 Jan;39(1):66-76.e1-2
pubmed: 20940029
Science. 2007 Nov 2;318(5851):798-801
pubmed: 17916692
Biol Reprod. 2010 Feb;82(2):363-72
pubmed: 19846602
Cell. 2013 Jan 31;152(3):390-3
pubmed: 23374336
EMBO Rep. 2000 Sep;1(3):244-52
pubmed: 11256607
J Cell Sci. 2010 May 15;123(Pt 10):1693-704
pubmed: 20427319
Recent Results Cancer Res. 2015;200:61-79
pubmed: 26376872
EMBO J. 1997 Apr 1;16(7):1785-94
pubmed: 9130722
Oncogene. 2001 Mar 22;20(12):1497-508
pubmed: 11313893
Nature. 1998 Apr 9;392(6676):569-74
pubmed: 9560153
Nature. 1990 May 31;345(6274):458-60
pubmed: 2342578