TRIM47 (Kr.17q25.1), GOA, RNF100, (CIV_SPRYPRY)
Tämä geeni on
yli-ilmentyvänä astrosytoomasta ja siitä tulee geenin toinen nimi
GOA.Geenillä on tärkeä paralogi samassa kromosomsia 17 ,TRIM25.
TRIM47:n
yliesiintyminen NSCLC-keuhkosyöpäkudosessa ( ei-pienisoluinen
keuhkosyöpä, eräs välikoko syöpäsolua) on negatiivinen
prognostinen tekijä.
Gene Overexpressed in Astrocytoma = GOA.
Geenin koodaamassa
proteiinisa on 638 aminohappoa.
Peptidirakenne
Artikkeleita_ Related articles in PubMed
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TRIM47 overexpression is a poor prognostic factor and contributes to carcinogenesis in non-small cell lung carcinoma. Han Y, et al. Oncotarget, 2017 Apr 4. PMID 28186994, Free PMC Article Key words: EMT,NSCLC, p53, TRIM47, Cell cycle.(Suomennosta): Tavallisimpia pahanlaatuisia tauteja, joihin littyvä morbiditeetti ja mortaliteetti ovat korkeita, on ei-pienisoluinen keuhkosyöpätyyppi NSCLC. Tutkijat havaitsivat, että TRIM47: n ilmentyminen oli suurempi tässä syöpäkudoksessa kuin lähellä olevassa normaalissa kudoksessa. TRIM47:n yli-ilmentyminen korreloi negatiivisesti prognoosiin tätä NSCLC- syöpää potevilla ja oli itsenäinen prognostinen merkitsijä. Tutkijat selvittivät syöpäsoluilla, mitä TRIM47:n poisto (depletio) keuhkosyöpäsolulinjasta vaikutti: se esti merkitsevästi soluproliferaatiota ja jarrutti solusyklin G1-vaiheeseen. Jos hiljennettiin TRIM47, estyi solun migraatio, invaasio ja tumorigeenisyys hiiressä. TRIM47:n ilmentyminen korreloi syöpään liittyviin prosesseihin ja signaaliteihin ( kuten p53-solusykli ja NFkB - epiteliaalisesta mesenkymaaliseen transitio (EMT)). TRIM47 omasi estovaikutusta p53 - tekijään ja edistävää vaikutusta NF-kB-tekijään ja nämä seikat jouduttivat tuumorin proliferoitumista ja etäpesäkkeiden muodostusta. Yhteenvetona TRIM47 toimii tuumorin onkogeeninä keuhkosyövässä ( Tutkittuna on ei-pienisoluien keuhkosyöpätyyppi). Tiedot antavat oivallusta TRIM47:n mahdolliseen biologiseen mekanismiin ei-pienisoluisen keuhkosyövän progressiossa ja valottavat siitä saatavaa hyötymahdollisuutta terapia- kohteena.
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Non-small cell lung carcinoma (NSCLC) is the most common malignancy with the highest morbidity and mortality. In this study, we found that tripartite motif containing 47 (TRIM47) expression level was higher in tumor tissues than in normal adjacent tissues. Overexpression of TRIM47 closely correlated with poor prognosis in patients with NSCLC. Multivariate Cox regression analyses showed that TRIM47 overexpression could be considered an independent prognostic factor for NSCLC. TRIM47 depletion significantly inhibited cell proliferation and induced G1phase arrest in A549 and H358 cell lines. Moreover, TRIM47 silencing remarkably inhibited cell migration, cell invasion, and tumorigenicity in nude mice. Gene set enrichment analysis (GSEA) revealed that cancer-related process and pathways, including p53-cell cycle and NFκB-epithelial mesenchymal transition (EMT) pathway, were significantly correlated with TRIM47 expression. Real-time PCR and Western blot analysis revealed that TRIM47 exerts an inhibitory effect on p53 and an facilitatory effect on NF-κB, thereby promoting tumor proliferation and metastasis. Taken together, TRIM47 acts as a tumor oncogene in NSCLC. Our data provide insight into the possible biological mechanism of TRIM47 in the progression of NSCLC and highlight its usefulness as a potential therapeutic target.
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Increased Expression of Tripartite Motif (TRIM) 47 Is a Negative Prognostic Predictor in Human Prostate Cancer. Fujimura T, et al. Clin Genitourin Cancer, 2016 Aug.(Suomennosta)Kohonneet TRIM47 ilmentymät ovat negatiivinen prognostinen merkitsijä prostatakarsinoomassa. TRIM47 saattaa olla uusi terapeuttinen kodhe.3. GOA, a novel gene encoding a ring finger B-box coiled-coil protein, is overexpressed in astrocytoma. Vandeputte DA, et al. Biochem Biophys Res Commun, 2001 Aug 24. PMID 11511098
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(Suomennosta) TRIM47 omaa myös nimen GOA, geeni, joka on yli-ilmentynyt astrosytoomassa 90%:ssa tapauksista. Geeniä ilmenee aivoissa. Munuaisissa sitä on hyvin runsaasti ja muuten ilmenemä on matala verrattuna aivossa ilmenevään tasoon.Immunohistokemiallisesti tumat värjäytyivät huomattavasti astrosytoomassa ja sikiöaikaisessa astrosyytissä, mutta värjäytymä oli poissa kypsästä astrosyytistä. Yli-ilmentyminen ei johtunut laajentumissta, koska vain yhdessä tapauksessa 65:stä oli tapahtunut geenin laajentuma (amplification). Geeni lokalisoitui alueeseen 17q24-25 ja se on alue, jossa useissa tuumoreissa tapahtuu funktion hankintamutaatiota tai geenin laajenemista. GOA sisältää motiivin LXXLL ja arvellaan sen olevan tumareseptorin sitoutumiskohta. Tässä tutkijat osoittavat, että GOA omaa tärkeän osuuden dedifferentiaatiossa, joka astrosytooman tumorigeneesiin liittyy – ehkä muihinkin tuumorityyppeihin.
( Ps. Havaitsin PubMed Gene, proteiini
GOA isoformirakenteesta nämä motiivit: LXXLL, LSELL, LQELL,
LLRRL. Kts. Rakenne)
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Serial analysis of gene expression (SAGE) was used to identify a gene named GOA (gene overexpressed in astrocytoma), which codes for a novel Ring finger B-box coiled-coil (RBCC) protein. Northern blot hybridization showed overexpression of GOA in 9 of 10 astrocytomas. Except for kidney, in which high expression was found, expression levels in normal tissues were low and comparable to normal brain. Immunohistochemistry demonstrated presence of GOA, with prominent nuclear staining, in astrocytoma tumor cells and astrocytes of fetal brain, but virtual absence in mature astrocytes. Overexpression was not due to amplification, since amplification of GOA was only found in one of 65 astrocytomas. GOA was localized to 17q24-25, a region that is frequently gained or amplified in a number of other tumor types. GOA contains two LXXLL motifs, which are thought to be important for nuclear receptor binding. Our data suggest an important role of GOA in the process of dedifferentiation that is associated with astrocytoma tumorigenesis and possibly with that of other tumor types as well.
TRIM45 ja TRIM65 geenien sijaintikohtaa tutkittu eurooppalaistaustaisilta . Onko assosioaatiota leukoaraioosiin vai ei?
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Genome-wide association studies of cerebral white matter lesion burden: the CHARGE consortium. Fornage M, et al. Ann Neurol, 2011 Jun. PMID 21681796, Free PMC Article OBJECTIVE:
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(Suomennosta) Koko genomia käsittivä assosiaatiotutkimuksia on tehty valkoisen aineksen vauriokertymistä. MRI-tutkimuksin voidaan havaita valkean aineen hyperintensiteettiä, mikä on osaa ikääntyvään aivoon liittyvästä verisuoniston vauriosta ja arvellaan sen heijastavat pienten, syvällä aivoissa olevien verisuonten iskemistä vauriota. Nämä valkean aineen hyperintensiteetit (WMH) liittyvät kohonneesen riskiin kognitiivisesta ja motorisesta toimintahäiriöstä, dementiasta, depressiosta ja halvauksesta. Vaikka perinnöllisyydellä on merkitsevyyttä, on tunnistettu vain hyvin harvoja geenikohtia, jotka saattaisivat vaikuttaa valkean aineen hyperintensiteettiä (WMH). Tutkijat stekivät genomilaajuisten assosiaatiotutkimusten meta-analyysin ( n= 9361 halvauspotilasta) . He tunnistivat kuusi uutta riskiin assosioituvaa yksittäistä nukelotidipolymorfiaa(SNP) geenistä 17 , kohdasta 17q25. Kyseessä olevat geenit olivat WBP2, TRIM65, TRIM47, MRPL38, FBF1 ja ACOX1. He määrittelivät tarkemmat sijainnit ja havaitsivat, että kohtien eri alleelit lisäsivät osaltaan hieman WMH kuormitusta koko populaatio-otoksen keskimääräisessä WMH-kuormituksessa. Tämä genominlaajuinen eurooppalaisväestön tutkimus valkean aineen hyperintensiteettirasitteesta tunnistaa kromosomista 17 uuden kohdan. Tämän kohdan jatkotarkastelu saattaa antaa lisäoivalluksia aivon valkoisen aineksen hyperintensiteettien patogeneesistä
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White matter hyperintensities (WMHs) detectable by magnetic resonance imaging are part of the spectrum of vascular injury associated with aging of the brain and are thought to reflect ischemic damage to the small deep cerebral vessels. WMHs are associated with an increased risk of cognitive and motor dysfunction, dementia, depression, and stroke. Despite a significant heritability, few genetic loci influencing WMH burden have been identified.METHODS: We performed a meta-analysis of genome-wide association studies (GWASs) for WMH burden in 9,361 stroke-free individuals of European descent from 7 community-based cohorts. Significant findings were tested for replication in 3,024 individuals from 2 additional cohorts. RESULTS: We identified 6 novel risk-associated single nucleotide polymorphisms (SNPs) in 1 locus on chromosome 17q25 encompassing 6 known genes including WBP2, TRIM65, TRIM47, MRPL38, FBF1, and ACOX1. The most significant association was for rs3744028 (p(discovery) = 4.0 × 10(-9) ; p(replication) = 1.3 × 10(-7) ; p(combined) = 4.0 × 10(-15) ). Other SNPs in this region also reaching genome-wide significance were rs9894383 (p = 5.3 × 10(-9) ), rs11869977 (p = 5.7 × 10(-9) ), rs936393 (p = 6.8 × 10(-9) ), rs3744017 (p = 7.3 × 10(-9) ), and rs1055129 (p = 4.1 × 10(-8) ). Variant alleles at these loci conferred a small increase in WMH burden (4-8% of the overall mean WMH burden in the sample). INTERPRETATION: This large GWAS of WMH burden in community-based cohorts of individuals of European descent identifies a novel locus on chromosome 17. Further characterization of this locus may provide novel insights into the pathogenesis of cerebral WMH
Mitä geenejä mainittiin TRIM47 ja TRIm65 ohella tästä geenikohdasta 17q25 ?
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WBP2 ( eli GRAMP),WW-domeeniin sitoutuva proteiini, transkriptionaalinen koaktivaattori ESR1- (estrogeeni) ja PGR (progesteroni)- reseptoreille
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MRPL38, mitokondriaalinen ribosomaalinen proteiini
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FBF1, Fas linking factor, Alb, Albatrosproteiini epiteliaalisen apikaalisen junktiokompleksin proteiini, mekitsee polarisoitumsielle. Ciliafunktiossa tärkeä.
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ACOX1 eli PALMCOX, peroxisomaalinen palmitiinihappoCoA oksidaasi. Betaoksidaation aloituksessa tärkeä.
Pohdittu TRIM47:n osuutta leukoaraioosiin kiinalaisväestössä.
- LEUKOARAIOOSI, ( aivojen valkean aineksen harventumat) Termiä selvittävä artikkeli löytyy netistä. "valkean ainaan läiskät"
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https://www.etlehti.fi/artikkeli/terveys/valkean-aineen-laiskat
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Analysis
of genetic polymorphisms associated with leukoaraiosis in the
southern Chinese population: A case-control study. Huang WQ, et
al. Medicine (Baltimore), 2016 Aug. PMID 27583843, Free
PMC Article
Iäkkäillä henkilöillä leukoaraioosi on tavallinen havainti MRI-tutkimuskessa. Prevalenssi vaihtelee 50- 100% välillä. Eruuppalaisten jälkeläisistä on havaittu useita LA:n epäiltyjä geenejä tai geneettisiä riskitekijöitä. Täsä artikkelissa raportoidaan ensimmäinen replikaatiotutkimus kiinalaisessa väestössä useista tavallisista ja uusista geenivarianteista. Tässä ei pidetä TRIM65 tai TRIM47 geenejä osallisina aivojen valkean aineen leukoaraioosiin.
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Leukoaraiosis (LA) is a frequent neuroimaging finding commonly observed on brain MRIs of elderly people with prevalence ranging from 50% to 100%. Multiple susceptibility genes or genetic risk factors for LA have been identified in subjects of European descent. Here, we report the first replication study on several common and novel genetic variations in the Chinese population. In this study, a total of 244 subjects (201 LA patients and 43 controls) were enrolled according to our new and strict definition for LA. Subsequently, 6 genetic variants at 5 genes, rs3744028 in TRIM65, rs1055129 in TRIM47, rs1135889 in FBF1, rs1052053 in PMF1, and rs1801133 (C677T) and rs1801131(A1298C) in MTHFR, were selected for genotyping using polymerase chain reaction (PCR)-based pyrosequencing and restriction fragment length polymorphism (RFLP) together with capillary electrophoresis (CE) and agarose gel electrophoresis. Finally, Pearson's χ and multivariate logistic regression tests were used to examine the associations between the genotypes and LA. Among these candidate polymorphisms, except for rs1052053 and rs1801131, rs1135889 (P = 0.012) showed significant associations with LA in the dominant model, and the other 3 SNPs, rs3744028 (P = 0.043), rs1055129 (P = 0.038), and rs1801133 (P = 0.027), showed significant associations with LA in the recessive model. However, these differences no longer remained significant after adjusting for age, gender, hypertension, and diabetes mellitus and applying Bonferroni correction or Sidak correction for multiple testing. These results suggest that the above-mentioned genetic variants are not associated with LA risk. In summary, the study did not replicate the susceptibility of rs3744028, rs1055129, and rs1135889 at the Chr17q25 locus for LA nor did it find any other significant results for rs1052053, rs1801133, and rs1801131 in the Chinese population. It strongly indicated the ethnic differences in the genetics of LA. However, the associations of rs3744028 (TRIM65), rs1055129 (TRIM47), rs1135889 (FBF1), and rs1801133 (MTHFR) with LA before Bonferroni correction and Sidak correction for multiple testing are worth highlighting. Thus, we believe that a genome-wide association study and candidate gene association studies are needed to reassess the previous findings and screen novel risk genes for LA in China. These results suggest that rs1055129 in TRIM47 is not associated with leukoaraiosis (LA) risk in the Chinese population. However, the association of rs1055129 (TRIM47) with LA before Bonferroni correction and Sidak correction is worth highlighting.
Peptidirakenne,
Huomaa kohta: 582: omega-N-metyyliarginiini- tällaista en ole huomannut TRIM-issa ennen.
Conserved Domains (3)
- pfam00643
Location:178 → 217 - zf-B_box; B-box zinc finger
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cd15808
Location:421 → 626 - SPRY_PRY_TRIM47; PRY/SPRY domain in tripartite motif-containing protein 47 (TRIM47), also known as RING finger protein 100 (RNF100) or Gene overexpressed in astrocytoma protein (GOA)
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cl17238
Location:9 → 57 - RING; RING-finger (Really Interesting New Gene) domain, a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc; defined by the 'cross-brace' motif C-X2-C-X(9-39)-C-X(1-3)- H-X(2-3)-(N/C/H)-X2-C-X(4-48)C-X2-C; probably involved in ...
tripartite motif-containing protein 47 [Homo sapiens]
NCBI Reference Sequence: NP_258411.2Identical Proteins FASTA Graphics
LOCUS NP_258411 638 aa linear PRI 13-MAR-2018 DEFINITION tripartite motif-containing protein 47 [Homo sapiens]. ACCESSION NP_258411 VERSION NP_258411.2 DBSOURCE REFSEQ: accession NM_033452.2 KEYWORDS RefSeq. SOURCE Homo sapiens (human) ORGANISM Homo sapiens Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo. REFERENCE 1 (residues 1 to 638) AUTHORS Han Y, Tian H, Chen P and Lin Q. TITLE TRIM47 overexpression is a poor prognostic factor and contributes to carcinogenesis in non-small cell lung carcinoma JOURNAL Oncotarget 8 (14), 22730-22740 (2017) PUBMED 28186994 REMARK GeneRIF: High TRIM47 expression is associated with non-small cell lung carcinoma. REFERENCE 2 (residues 1 to 638) AUTHORS Huang WQ, Ye HM, Li FF, Yi KH, Zhang Y, Cai LL, Lin HN, Lin Q and Tzeng CM. TITLE Analysis of genetic polymorphisms associated with leukoaraiosis in the southern Chinese population: A case-control study JOURNAL Medicine (Baltimore) 95 (35), e3857 (2016) PUBMED 27583843 REMARK GeneRIF: These results suggest that rs1055129 in TRIM47 is not associated with leukoaraiosis (LA) risk in the Chinese population. However, the association of rs1055129 (TRIM47) with LA before Bonferroni correction and Sidak correction is worth highlighting. REFERENCE 3 (residues 1 to 638) AUTHORS Fujimura T, Inoue S, Urano T, Takayama K, Yamada Y, Ikeda K, Obinata D, Ashikari D, Takahashi S and Homma Y. TITLE Increased Expression of Tripartite Motif (TRIM) 47 Is a Negative Prognostic Predictor in Human Prostate Cancer JOURNAL Clin Genitourin Cancer 14 (4), 298-303 (2016) PUBMED 26873435 REMARK GeneRIF: Study shows that protein and gene expression level of TRIM47 are up-regulated in prostate neoplasm. REFERENCE 4 (residues 1 to 638) AUTHORS Fornage M, Debette S, Bis JC, Schmidt H, Ikram MA, Dufouil C, Sigurdsson S, Lumley T, DeStefano AL, Fazekas F, Vrooman HA, Shibata DK, Maillard P, Zijdenbos A, Smith AV, Gudnason H, de Boer R, Cushman M, Mazoyer B, Heiss G, Vernooij MW, Enzinger C, Glazer NL, Beiser A, Knopman DS, Cavalieri M, Niessen WJ, Harris TB, Petrovic K, Lopez OL, Aund T, Romero JR, Rice K, Taylor KD, Nalls MA, Rotter JI, Sharrett R, van Duijn CM, Amouyel P, Wolf PA, Gudnason V, van der Lugt A, Boerwinkle E, Psaty BM, Seshadri S, Tzourio C, Breteler MM, Mosley TH, Schmidt R, Longstreth WT, DeCarli C and Launer LJ.u R, Lambert JC, Hofman A, Gottesman RF, Garcia M, Heckbert SR, Atwood LD, Catellier DJ, Uitterlinden AG, Yang Q, Smith NL, Aspel TITLE Genome-wide association studies of cerebral white matter lesion burden: the CHARGE consortium JOURNAL Ann. Neurol. 69 (6), 928-939 (2011) PUBMED 21681796 REFERENCE 5 (residues 1 to 638) AUTHORS Beausoleil SA, Villen J, Gerber SA, Rush J and Gygi SP. TITLE A probability-based approach for high-throughput protein phosphorylation analysis and site localization JOURNAL Nat. Biotechnol. 24 (10), 1285-1292 (2006) PUBMED 16964243 REFERENCE 6 (residues 1 to 638) AUTHORS Vandeputte DA, Meije CB, van Dartel M, Leenstra S, IJlst-Keizers H, Das PK, Troost D, Bosch DA, Baas F and Hulsebos TJ. TITLE GOA, a novel gene encoding a ring finger B-box coiled-coil protein, is overexpressed in astrocytoma JOURNAL Biochem. Biophys. Res. Commun. 286 (3), 574-579 (2001) PUBMED 11511098 COMMENT VALIDATED REFSEQ: This record has undergone validation or preliminary review. The reference sequence was derived from AY026763.1 and BG385464.1. On Oct 28, 2004 this sequence version replaced NP_258411.1. ##Evidence-Data-START## Transcript exon combination :: AY026763.1, SRR1163657.572553.1 [ECO:0000332] RNAseq introns :: single sample supports all introns SAMEA1968968, SAMEA2151358 [ECO:0000348] ##Evidence-Data-END## FEATURES Location/Qualifiers source 1..638 /organism="Homo sapiens" /db_xref="taxon:9606" /chromosome="17" /map="17q25.1" Protein 1..638 /product="tripartite motif-containing protein 47" /note="RING finger protein 100; gene overexpressed in astrocytoma protein" /calculated_mol_wt=69401 Region 9..57 /region_name="RING" /note="RING-finger (Really Interesting New Gene) domain, a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc; defined by the 'cross-brace' motif C-X2-C-X(9-39)-C-X(1-3)- H-X(2-3)-(N/C/H)-X2-C-X(4-48)C-X2-C; probably involved in...; cl17238" /db_xref="CDD:302633" Site order(9,12,24,26,29,32,54,57) /site_type="other" /note="cross-brace motif" /db_xref="CDD:238093" Site 72 /site_type="phosphorylation" /experiment="experimental evidence, no additional details recorded" /note="Phosphothreonine. {ECO:0000250|UniProtKB:Q8C0E3}; propagated from UniProtKB/Swiss-Prot (Q96LD4.2)" Region 178..217 /region_name="zf-B_box" /note="B-box zinc finger; pfam00643" /db_xref="CDD:279037" Site order(182,185,204,209) /site_type="other" /note="Zn2+ binding site [ion binding]" /db_xref="CDD:237988" Region 421..626 /region_name="SPRY_PRY_TRIM47" /note="PRY/SPRY domain in tripartite motif-containing protein 47 (TRIM47), also known as RING finger protein 100 (RNF100) or Gene overexpressed in astrocytoma protein (GOA); cd15808" /db_xref="CDD:293980" Site 461 /site_type="phosphorylation" /experiment="experimental evidence, no additional details recorded" /note="Phosphoserine. {ECO:0000244|PubMed:16964243}; propagated from UniProtKB/Swiss-Prot (Q96LD4.2)" Site 582 /site_type="methylation" /experiment="experimental evidence, no additional details recorded" /note="Omega-N-methylarginine. {ECO:0000244|PubMed:24129315}; propagated from UniProtKB/Swiss-Prot (Q96LD4.2)" Site 588 /site_type="phosphorylation" /experiment="experimental evidence, no additional details recorded" /note="Phosphoserine. {ECO:0000244|PubMed:17081983, ECO:0000244|PubMed:23186163, ECO:0000244|PubMed:24275569}; propagated from UniProtKB/Swiss-Prot (Q96LD4.2)" CDS 1..638 /gene="TRIM47" /gene_synonym="GOA; RNF100" /coded_by="NM_033452.2:28..1944" /db_xref="CCDS:CCDS32737.1" /db_xref="GeneID:91107" /db_xref="HGNC:HGNC:19020" /db_xref="MIM:611041" ORIGIN 1 mdgsgpfscp icleplrepv tlpcghnfcl aclgalwphr gasgaggpgg aarcplcqep 61 fpdglqlrkn htlsellqlr qgsgpgsgpg papalapeps apsalpsvpe psapcapepw 121 pageepvrcd acpegaalpa alsclsclas fcpahlgphe rspalrghrl vpplrrlees 181 lcprhlrple rycraervcl ceacaaqehr ghelvpleqe ralqeaeqsk vlsavedrmd 241 elgagiaqsr rtvaliksaa vaerervsrl fadaaaalqg fqtqvlgfie egeaamlgrs 301 qgdlrrqeeq rsrlsrarqn lsqvpeadsv sflqellalr laledgcgpg pgpprelsft 361 kssqavravr dmlavacvnq weqlrgpggn edgpqkldse adaepqdles tnlleseapr 421 dyflkfayiv dldsdtadkf lqlfgtkgvk rvlcpinypl sptrfthceq vlgegaldrg 481 tyyweveiie gwvsmgvmae dfspqepydr grlgrnahsc clqwngrsfs vwfhgleapl 541 phpfsptvgv cleyadrala fyavrdgkms llrrlkasrp rrggipaspi dpfqsrldsh 601 faglfthrlk pafflesvda hlqigplkks cisvlkrr //
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