TRIM58 ( Kr.1q44) vaikuttaa punasolun tumattomuuden erytropoieesin loppuvaiheessa

TRIM 58, kr.1q44

Tämä geeni indusoituu myöhäisvaiheessa erytropoieesia ja proteiini ubikitinoi mikrotubulisen moottorin dyneiinin DYNC1LI1/DYNC1IL2 ja stimuloi dyneiiniholoproteiinikompleksin degradaatiota. Saattaa osallistua erytroblastin enukleaatioprosessiin säätelemällä nukleaarista polarisaatiota.Epigeneettinen modifikaatio, metyloituminen, korreloi ikään ja TRIM58 kuuluu ikään korreloituviin geeneihin joita foidaan forenssisessa tieteessä hyödyntää iän arvioimisessa. Eräissä syövissä  TRIM58 on metyloitunut ( keuhkosyövän alkuvaihe, maksasolusyöpä).

Lähde 1.

http://www.genecards.org/cgi-bin/carddisp.pl?gene=TRIM58

GeneCards Summary for TRIM58 Gene TRIM58 (Tripartite Motif Containing 58) is a Protein Coding gene. GO annotations related to this gene include ligase activity. An important paralog of this gene is TRIM11.

UniProtKB/Swiss-Prot for TRIM58 Gene

• TRI58_HUMAN,Q8NG06
  

• E3 ubiquitin ligase induced during late erythropoiesis. Directly binds and ubiquitinates the intermediate chain of the microtubule motor dynein (DYNC1LI1/DYNC1LI2), stimulating the degradation of the dynein holoprotein complex. May participate in the erythroblast enucleation process through regulation of nuclear polarization.

Lähde 2. Aminohapporakenne  1-486.

http://www.uniprot.org/blast/?about=Q8NG06[1-486]&key=Chain&id=PRO_0000272301

Proteiini 1-486 peptidirakenne

>sp|Q8NG06|1-486

MAWAPPGERL­REDARCPVCL­DFLQEPVSVD­CGHSFCLRCI­SEFCEKSDGA­QGGVYACPQC­

RGPFRPSGFR­PNRQLAGLVE­SVRRLGLGAG­PGARRCARHG­EDLSRFCEED­EAALCWVCDA­

GPEHRTHRTA­PLQEAAGSYQ­VKLQMALELM­RKELEDALT­QEANVGKKTV­IWKEKVEMQR­Q

RFRLEFEKH­RGFLAQEEQR­QLRRLEAEERA­TLQRLRESKS­RLVQQSKALK­ELADELQERC­

QRPALGLLEG­VRGVLSRSKA­VTRLEAENIP­MELKTACCIP­GRRELLRKFQ­VDVKLDPATA­

HPSLLLTADL­RSVQDGEPWR­DVPNNPERFD­TWPCILGLQS­FSSGRHYWEV­LVGEGAEWGL­

GVCQDTLPRK­GETTPSPENG­VWALWLLKGN­EYMVLASPSV­PLLQLESPRC­IGIFLDYEAG­

EISFYNVTDG­SYIYTFNQLF­SGLLRPYFFI­CDATPLILPP­TTIAGSGNWA­SRDHLDPASD­

VRDDHL­

Lähde 3. TRIM 58 on tärkeä tekijä kypsän punasolun muodostumisessa.

https://www.ncbi.nlm.nih.gov/pubmed/25241935

Dev Cell. 2014 Sep 29;30(6):688-700. doi: 10.1016/j.devcel.2014.07.021. Epub 2014 Sep 18.

Trim58 degrades Dynein and regulates terminal erythropoiesis.

Thom CS¹, Traxler EA¹, Khandros E¹, Nickas JM², Zhou OY², Lazarus JE³, Silva AP⁴, Prabhu D², Yao Y², Aribeana C², Fuchs SY⁵, Mackay JP⁴, Holzbaur EL⁶, Weiss MJ

TRIM58 is an E3 ubiquitin ligase superfamily member implicated by genome-wide association studies to regulate human erythrocyte traits. Here, we show that Trim58 expression is induced during late erythropoiesis and that its depletion by small hairpin RNAs (shRNAs) inhibits the maturation of late-stage nucleated erythroblasts to anucleate reticulocytes. Imaging flow cytometry studies demonstrate that Trim58 regulates polarization and/or extrusion of erythroblast nuclei. In vitro, Trim58 directly binds and ubiquitinates the intermediate chain of the microtubule motor dynein. In cells, Trim58 stimulates proteasome-dependent degradation of the dynein holoprotein complex. During erythropoiesis, Trim58 expression, dynein loss, and enucleation occur concomitantly, and all are inhibited by Trim58 shRNAs. Dynein regulates nuclear positioning and microtubule organization, both of which undergo dramatic changes during erythroblast enucleation. Thus, we propose that Trim58 promotes this process by eliminating dynein. Our findings identify an erythroid-specific regulator of enucleation and elucidate a previously unrecognized mechanism for controlling dynein activity.

Lähde 4. TRIM 58 tuumorisuppressorigeenikandidaatti alkavassa keuhkosyövässä

https://www.ncbi.nlm.nih.gov/pubmed/27926516

Oncotarget. 2017 Jan 10;8(2):2890-2905. doi: 10.18632/oncotarget.13761.

Frequent silencing of the candidate tumor suppressor TRIM58 by promoter methylation in early-stage lung adenocarcinoma.

Kajiura K^1,2, Masuda K¹, Naruto T¹, Kohmoto T¹, Watabnabe M¹, Tsuboi M², Takizawa H², Kondo K³, Tangoku A², Imoto I¹.

Lähde 5. TRIM58 maksasolusyövässä metyloitunut

Oncol Rep. 2016 Aug;36(2):811-8. doi: 10.3892/or.2016.4871. Epub 2016 Jun 13.

Aberrant methylation of TRIM58 in hepatocellular carcinoma and its potential clinical implication.

Qiu X¹, Huang Y¹, Zhou Y¹, Zheng F¹.Abstract

TRIM58 (tripartite motif containing 58) has been reported as a novel methylated gene in hepatocellular carcinoma (HCC) by methylation microarrays. However, its associations with mRNA expression and clinicopathological characteristics have not been evaluated. In this study, we explored the potential clinical implications of TRIM58 methylation in HCC. We analyzed the methylation level of TRIM58 in 181 HCC tissues, 172 matched adjacent non-tumor tissues and 13 normal liver tissues using methylation-sensitive restriction enzyme based quantitative PCR and bisulfite genomic sequencing. Further, the mRNA expression level of TRIM58 was measured in 46 paired HCC and adjacent non-tumor tissues by quantitative real-time PCR. Moreover, the relationship between TRIM58 methylation and mRNA expression, the clinicopathological features, as well as prognostic value were evaluated. The results showed that TRIM58 methylation was significantly higher in HCC tissues compared with adjacent non-tumor tissues and normal liver tissues (both p<0 .0001="" b="">Using 10% as the cut-off value, hypermethylation of TRIM58 was specific in HCC tissues (28.18%, 51/181), with a tendency to correlate with unfavorable disease-free survival (p=0.047). Moreover, TRIM58 expression was significantly decreased in HCC tissues compared with adjacent non-tumor tissues (p<0 .0001="" b=""><0 .0001="" a="" after="" and="" application="" associated="" association="" be="" clinical="" common="" contribute="" data="" dfs="" dna="" downregulation="" event="" expression.="" further="" furthermore="" hcc="" hepatectomy.="" however="" hypermethylation="" in="" indicate="" investigated.="" is="" its="" may="" methylation="" mrna="" need="" negative="" of="" our="" p="" potential="" rs=" -0.260)." showed="" tends="" that="" the="" to="" trim58="" with="" worse="">

Lähde. 6. Ihmisen ikä assosioituu epigeneettiseen modifikaatioon. Tämä näkyy mm TRIM58 geenissä.

https://www.ncbi.nlm.nih.gov/pubmed/27108355

Forensic Sci Int. 2016 Jul;264:132-8. doi: 10.1016/j.forsciint.2016.03.047. Epub 2016 Apr 14.

The EpiTect Methyl qPCR Assay as novel age estimation method in forensic biology.

Mawlood SK¹, Dennany L², Watson N³, Pickard BS⁴.

Human aging is associated with epigenetic modification of the genome. DNA methylation at cytosines appears currently as the best characterised modification that occurs during the mammalian lifetime. Such methylation changes at regulatory region can provide insights to track contributor age for criminal investigation. The EpiTect Methyl II PCR system (QIAGEN) was used to compare methylation levels of CpG islands in the promoter regions of a number of age related genes, of which four successfully showed changes across the lifespan (NPTX2, KCNQ1DN, GRIA2 and TRIM58). This technique is based on the detection of remaining input genome after digestion with a methylation-sensitive restriction enzyme. This study examined DNA specimens from 80 female subjects of various ages (18-91 years) obtained from blood, using primers designed to flank the studied gene loci. The data obtained from DNA methylation quantification showed successful discrimination among volunteered ages. Overall, the difference between predicted and real age was about 11 years and absolute mean differences (AMD) was only 7.2 years error. We suggest the EpiTect system can be used as fast and simple innovative tool in future forensic age estimation. KEYWORDS: Aging; CpG Island; DNA methylation; Epigenetics; Gene promoter; Methylation-sensitive restriction

Lisäartikkelita PubMed lähteessä:

Related articles in PubMed

1. Frequent silencing of the candidate tumor suppressor TRIM58 by promoter methylation in early-stage lung adenocarcinoma. Kajiura K, et al. Oncotarget, 2017 Jan 10. PMID 27926516, Free PMC Article
2. Trim58 degrades Dynein and regulates terminal erythropoiesis. Thom CS, et al. Dev Cell, 2014 Sep 29. PMID 25241935, Free PMC Article
3. Seventy-five genetic loci influencing the human red blood cell. van der Harst P, et al. Nature, 2012 Dec 20. PMID 23222517, Free PMC Article Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P < 10(-8), which together explain 4-9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.
4. New gene functions in megakaryopoiesis and platelet formation. Gieger C, et al. Nature, 2011 Nov 30. PMID 22139419, Free PMC Article
5. Genome-wide association study of hematological and biochemical traits in a Japanese population. Kamatani Y, et al. Nat Genet, 2010 Mar. PMID 20139978

GeneRIFs: Gene References Into Functions

1. Our findings suggest that aberrant inactivation of TRIM58 consequent to CGI hypermethylation might stimulate the early carcinogenesis of LADC regardless of smoking status; furthermore, TRIM58 methylation might be a possible early diagnostic and epigenetic therapeutic target in LADC.

Muistiin geenistä TRIM58 ( proteiini B1A2)joka sijaitse kromosomissa 1 kohdassa  1q44.

 Sen tärkeä paralogi on TRIM11 (proteiini B1A1). Sijaitsee kormosomissa 1, 1q42,13.

20.3. 2018
 Kromosomi 1:n  TRIM-proteiineja