kromosomi 11: TRIM5alfa-geeni . Muut TRIM geenit.

Interferonit säätelevät transkriptionaalisesti retroviruksen restriktiotekijää TRIM5 alfa.

LÄHDE:

Biochem Biophys Res Commun. 2005 Dec 30;338(4):1950-6. Epub 2005 Nov 11. A retrovirus restriction factor TRIM5alpha is transcriptionally regulated by interferons.

Asaoka K, Ikeda K, Hishinuma T, Horie-Inoue K, Takeda S, Inoue S.

Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical School, Saitama, Japan.

TIIVISTELMÄ 

• Tripartiitti-motiivinen proteiiniperhe, retroviraalisen infektion restriktiotekijöihiin kuuluva

Abstract

• TRIM5alpha is a member of tripartite motif protein family and recently identified as a restriction factor for retroviral infection in a species-specific manner.

• Ihmisen TRIM5alfageeni sijaitseee kromosomissa 11, asemassa 11p15 rykelmänä muitten TRIM-geenien kanssa ja niihin kuuluu TRIM6, TRIM21 ja TRIM24.

Human TRIM5alpha gene is located on chromosomal position 11p15 in a cluster with other TRIM genes including TRIM6, 21, 22, and 34.

•  Interferoni (IFN) säätää ylös TRIMalfa mRNA expresion koejärjestelmissä.

We show here that interferon (IFN) upregulates TRIM5alpha mRNA expression in HeLa and HepG2 cells by performing Northern blot analysis and quantitative real-time PCR.

•  Interferoni aiheutti TRIM5alfa promoottorissa aktivaation.

TRIM5alpha promoter activity was IFN inducible as confirmed by luciferase assay using a reporter plasmid that contained the 5'-flanking region of TRIM5alpha.

•  Interferoni IFN aktivoi TRIM5alfan promototorin IFN:llä stimuloidun ISRE elementin vasteen  kautta.

Mutational analysis has revealed that IFNs activate TRIM5alpha promoter activity through a putative interferon-stimulated response element (ISRE).

•  ISRE-sekvenssiin kiinnittyy toinenkin  interferoniin vastaava  signaalinjohtaja ja transkriptiotekijän(STAT1) aktivaattori.

Intriguingly, another IFN-responsive protein signal transducer and activator of transcription factor 1 (STAT1) binds to the ISRE sequence as shown by electrophoretic mobility shift assay using HeLa cell extracts.

• TRIM5alfa-proteiinin ilmeneminen induosituu  beta-interferonilla(IFNbeta) .

We have raised a specific polyclonal antibody against TRIM5alpha and confirmed that TRIM5alpha protein expression is inducible by IFN-beta in HeLa cells.

•  Näistä tutkimuksista päätellen TRIM5alfan transkriptio ja proteiinisynteesi voi moduloitua interferonilla, joten TRIM5alfalla saattaa olla osaa IFN:n indusoimassa antivirustilassa, joka kehittyy retrovirusinfektiossa.

These results lead us to define that the transcription and protein synthesis of TRIM5alpha could be modulated by IFN, suggesting that TRIM5alpha may play a role in an IFN-induced antiviral state against retrovirus infection.

Suom. 20.11. 2013.