Review on WRAP53 (WD repeat containing, antisense to TP53), with data on DNA, on the protein encoded, and where the gene is implicated

Farnebo, M

Atlas of Genetics and Cytogenetics in Oncology and Haematology

I-Revues

   
 
 
 
 
 
Gene Section 
Mini Review 
 
Atlas Genet Cytogenet Oncol Haematol. 2011; 15(7)  596 
Atlas of Genetics and Cytogenetics 
in Oncology and Haematology 
OPEN ACCESS JOURNAL AT INIST-CNRS 
WRAP53 (WD repeat containing, antisense to 
TP53) 
Marianne Farnebo 
Karolinska Institutet, Cancer Center Karolinska (CCK) R8 :04, 17176 Stockholm, Sweden (MF) 
 
Published in Atlas Database: November 2010 
Online updated version : http://AtlasGeneticsOncology.org/Genes/WRAP53ID50705ch17p13.html 
DOI: 10.4267/2042/45986 
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence. 
© 2011 Atlas of Genetics and Cytogenetics in Oncology and Haematology 
 
Identity 
Other names: FLJ10385; TCAB1; WDR79 
HGNC (Hugo): WRAP53 
Location: 17p13.1 
DNA/RNA 
Description 
The WRAP53 gene encompasses 16 kb of DNA; 13 
exons (three non-coding alternative start exons: exon 
1alpha, 1beta and 1gamma. Exon 1alpha directly 
overlaps the first exon of TP53 in an antisense fashion 
by up to 227 base pairs (bp), depending on transcription 
start site (TSS) usage. Exon 1gamma of WRAP53 is 
located in the first intron of TP53 overlapping the 
previously identified transcript Hp53int1 in an 
antisense fashion. 
Transcription 
At least 17 splice variants. 1.9 kb mRNA; 1647 bp 
open reading frame. 
Regulatory antisense RNA 
Expression: widely expressed at low levels. 
Localisation: cytoplasm and nucleus. 
Function: regulates p53 mRNA levels by interacting 
with the 5'UTR of p53 mRNA. 
Homology: conserved in mouse. 
Diseases implication currently not analysed. 
Pseudogene 
Not known. 
 
 
 
 
Protein 
Description 
548 amino acids; 75 kDa protein; contains from N-term 
to C-term, a proline-rich region (aa 8-57), a WD40 
domain, 5 repeats (160-441), and a glycin-rich region 
(533-545). 
Expression 
Widely expressed, overexpressed in cancer. 
Localisation 
Cytoplasm and nucleus (enriched in Cajal bodies). 
Function 
Essential for Cajal body formation and maintenance. 
Targets the SMN complex, scaRNAs and telomerase 
enzyme (via TERC) to Cajal bodies. Inhibition of 
WRAP53 triggers mitochondrial-dependent apoptosis 
specifically in cancer cells. 
Homology 
Highly-conserved in mammals, the WD40 domain is 
conserved from human to fly. 
Mutations 
Note 
Single nucleotide polymorphisms (SNPs) in women 
with breast cancer (see below). 
Germinal 
Not reported. 
 
 
 
 
WRAP53 (WD repeat containing, antisense to TP53) Farnebo M 
 
 
 
 
 
Atlas Genet Cytogenet Oncol Haematol. 2011; 15(7)  597 
Somatic 
Not reported. 
Implicated in 
Breast and ovarian cancer 
Note 
Single nucleotide polymorphisms (SNPs) in WRAP53 
were found to be overrepresented in women with breast 
cancer, in particular estrogen receptor negative breast 
cancer. The same SNPs were also associated with 
aggressive ovarian cancer. The SNPs are located in the 
coding region of WRAP53 and results in the amino 
acid change R68G. 
Spinal muscular atrophy (SMA) 
Note 
WRAP53 targets the SMN complex to Cajal Bodies. 
WRAP53 and SMN association is disrupted in SMA 
patients suggesting a role of WRAP53 in SMA 
pathogenesis. 
Disease 
Spinal muscular atrophy (SMA) is a common 
neurodegenerative disorder caused by reduced levels of 
SMN due to mutations or deletions of the SMN1 gene. 
SMA is the leading genetic cause of infant mortality 
worldwide, affecting approximately 1 in 6000 infants. 
References 
Garcia-Closas M, Kristensen V, Langerød A, Qi Y, Yeager M, 
Burdett L, Welch R, Lissowska J, Peplonska B, Brinton L, 
Gerhard DS, Gram IT, Perou CM, Børresen-Dale AL, Chanock 
S. Common genetic variation in TP53 and its flanking genes, 
WDR79 and ATP1B2, and susceptibility to breast cancer. Int J 
Cancer. 2007 Dec 1;121(11):2532-8 
Mahmoudi S, Henriksson S, Corcoran M, Méndez-Vidal C, 
Wiman KG, Farnebo M. Wrap53, a natural p53 antisense 
transcript required for p53 induction upon DNA damage. Mol 
Cell. 2009 Feb 27;33(4):462-71 
Schildkraut JM, Goode EL, Clyde MA, Iversen ES, Moorman 
PG, Berchuck A, Marks JR, Lissowska J, Brinton L, Peplonska 
B, Cunningham JM, Vierkant RA, Rider DN, Chenevix-Trench 
G, Webb PM, Beesley J, Chen X, Phelan C, Sutphen R, 
Sellers TA, Pearce L, Wu AH, Van Den Berg D, Conti D, Elund 
CK, Anderson R, Goodman MT, Lurie G, Carney ME, 
Thompson PJ, Gayther SA, Ramus SJ, Jacobs I, Krüger Kjaer 
S, Hogdall E, Blaakaer J, Hogdall C, Easton DF, Song H, 
Pharoah PD, Whittemore AS, McGuire V, Quaye L, Anton-
Culver H, Ziogas A, Terry KL, Cramer DW, Hankinson SE, 
Tworoger SS, Calingaert B, Chanock S, Sherman M, Garcia-
Closas M. Single nucleotide polymorphisms in the TP53 region 
and susceptibility to invasive epithelial ovarian cancer. Cancer 
Res. 2009 Mar 15;69(6):2349-57 
Tycowski KT, Shu MD, Kukoyi A, Steitz JA. A conserved 
WD40 protein binds the Cajal body localization signal of 
scaRNP particles. Mol Cell. 2009 Apr 10;34(1):47-57 
Venteicher AS, Abreu EB, Meng Z, McCann KE, Terns RM, 
Veenstra TD, Terns MP, Artandi SE. A human telomerase 
holoenzyme protein required for Cajal body localization and 
telomere synthesis. Science. 2009 Jan 30;323(5914):644-8 
Mahmoudi S, Henriksson S, Weibrecht I, Smith S, Söderberg 
O, Strömblad S, Wiman KG, Farnebo M. WRAP53 is essential 
for Cajal body formation and for targeting the survival of motor 
neuron complex to Cajal bodies. PLoS Biol. 2010 Nov 
2;8(11):e1000521 
Mahmoudi S, Henriksson S, Farnebo L, Roberg K, Farnebo M.. 
WRAP53 promotes cancer cell survival and is a potential target 
for cancer therapy. Cell Death Dis. 
2011;2:e114;doi:10.1038/cddis.2010.90. 
This article should be referenced as such: 
Farnebo M. WRAP53 (WD repeat containing, antisense to 
TP53). Atlas Genet Cytogenet Oncol Haematol. 2011; 
15(7):596-597. 


WRAP53 (WD repeat containing, antisense to TP53)

http://documents.irevues.inist.fr/bitstream/2042/45986/2/11-2010-WRAP53ID50705ch17p13.pdf

WRAP53 (WD repeat containing, antisense to TP53)

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