TRIM27 (Kr.6p22.1), RFP, RNF76. (Alaryhmä C IV PRY/SPRY) Atyyppinen PTEN-polyubikitinaatio

 

• ( RINGfingerproteiinien luettelossa on lähemmä 200-300 RNF. Keräsin niitten luettelosta  227 RNF ja pienempi osa niistä on myös TRIM-proteiineja (tripartite motif). 

• Lisäksi näillä  TRIM-proteiineilla ja geeneillä   on  muitakin nimiä, jotka tulevat esim proteiinifunktiosta käsin lyhennelmänä ja sen takia ovat helpompia muistaa, mutta jos tämä rakennenimi jää pois, ei tule mieleen että ne kaikki voivat kuulua johonkin tiettyyn karttaan metaboliassa. Sellaisesta kartasta on miniatyyriyksityiskohtia kyllä sieltä täältä  löydettävissä)  

• TRIM27 omaa myös nimen RFP, Ret  finger protein

TRIM27, (Kr.6p22.1), RFP, RNF76 ( C IV alaryhmä, PRY/SPRY)

Paralogi TRIM7

Tällä TRIM27-proteiinilla on rakenne kuten CIV alaluokan TRIMeillä. RING, B-box1, B-box2, C-C domeeni ja C-terminaalissa PRY/SPRY. Tämä proteiini sijoittautuu nukleaariseen matrixiin. Se tekee interaktiota polycomb-proteiinin vahvistajan kanssa  ja vaimentaa geenitranskriptiota.  Sen arvellaan myös  osallistuvan miesten itusolujen erilaistumiseen .RFP voi olla kemoresistessin merkitsijä joisain syöpätyypeissä. 

Rakenteesta enemmän: https://www.ncbi.nlm.nih.gov/protein/NP_006501.1

https://www.ncbi.nlm.nih.gov/gene/5987

• Summary This gene encodes a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. This protein localizes to the nuclear matrix. It interacts with the enhancer of polycomb protein and represses gene transcription. It is also thought to be involved in the differentiation of male germ cells. Fusion of the N-terminus of this protein with the truncated C-terminus of the RET gene product has been shown to result in production of the ret transforming protein. [provided by RefSeq, Jul 2008]

Expression

Ubiquitous expression in thyroid (RPKM 14.7), spleen (RPKM 14.3) and 25 other tissues See more

Orthologs

mouse all

Related articles in PubMed

1. Serous versus high-grade endometrioid endometrial carcinoma: immunohistochemistry of RFP is not useful for differentiation. Ussakli C, et al. Pol J Pathol, 2016. PMID 28155970
2. Downregulation of TRIM27 expression inhibits the proliferation of ovarian cancer cells in vitro and in vivo. Ma Y, et al. Lab Invest, 2016 Jan. PMID 26568293
3. Expression of RET finger protein predicts chemoresistance in epithelial ovarian cancer. Horio M, et al. Cancer Med, 2012 Oct. PMID 23342271, Free PMC Article
   Resistance to platinum- and taxane-based chemotherapy is a major cause of treatment failure in ovarian cancer. Thus, it is necessary to develop a predictive marker and molecular target for overcoming drug resistance in ovarian cancer treatment. In a previous report, using an in vitro model, we found that the RET finger protein (RFP) (also known as tripartite motif-containing protein 27, TRIM27) confers cancer cell resistance to anticancer drugs. However, the significance of RFP expression in cancer patients remains elusive. In this study, we showed that RFP was expressed in 62% of ovarian cancer patients and its positivity significantly correlated with drug resistance. Consistent with clinical data, depletion of RFP by RNA interference (RNAi) in ovarian cancer cell lines, SKOV3 and HEY, significantly increased carboplatin- or paclitaxel-induced apoptosis and resulted in reduced anticancer drug resistance. In a nude mouse tumor xenograft model, inoculated RFP-knockdown ovarian cancer cells exhibited lower carboplatin resistance than control cells. These findings suggest that RFP could be a predictive marker for chemoresistance in ovarian cancer patients and also a candidate for a molecular-targeted agent. 
4. RET finger protein expression in invasive breast carcinoma: relationship between RFP and ErbB2 expression. Tezel GG, et al. Pathol Res Pract, 2009. PMID 19232840
5. Differential expression of RET finger protein in testicular germ cell tumors. Tezel G, et al. Pathol Int, 2002 Oct. PMID 12445133
   

See all (84) citations in PubMed
See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

1. RFP scores were higher both in serous and grade 3 endometrioid carcinoma (p > 0.05), and significantly lower in grade 1 endometrioid carcinoma (p < 0.05).
2. Studied the expression of TRIM27 in normal ovarian and fallopian tube epithelial cells and in ovarian serous carcinoma cells; correlated TRIM27 expression with clinical and pathological parameters.
3. Study found that compared to healthy individuals, Trim27 was significantly upregulated in patients with Parkinson's disease
4. The neoplasm leading cell specific expression of integrin beta1 was posttranscriptionally regulated by the TRIM27/MRTF-B complex in response to the loss of intercellular adhesion.
5. Authors observed rapid, ICP0-dependent loss of TRIM27 during HSV-1 infection.

• RFP-knockdown ovarian cancer cells exhibited lower carboplatin resistance than control cells. These findings suggest that RFP could be a predictive marker for chemoresistance in ovarian cancer patients.

• RFP-mediated ubiquitination of PTEN modulates its effect on AKT activation.

(Suomennosta tiivistelmästä) Tuumorisuppressori PTEN on lipidifosfataasi, jolla on keskeinen osuus PI3K-signaalitransduktiokaskadissa. Kuitenkin PTEN-aktiivisuuden säätöä solussa tarvitsee tarkemmin selvitellä.

Aiemmin on kyllä osoitettu, että PTEN-molekyylin ubikitinaatio saattaa moduloida sen stabiiliutta ja lokalisoitumista solussa, mutta kuitenkin on todettava, että ubikitinaation osuus on PTEN-funktiossa kaikkein kriittisintä sen fosfataasiaktiivisuudelle ja tähän kohtaan ei ole aiemmin pureuduttu. Tässä otsikon työssä tunnistetaan PTEN-proteiinin uusi E3-ubikitiiniligaasi, Ret finger-proteiini (RFP) eli TRIM27, toiselta nimeltä RFP, ja se kykenee edistämään PTENin epätyypillistä polyubikitinaatiota. Nämä ubikitinaatiot eivät kuitenkaan johda PTENin epästabiiliuteen tai uudelleen sijoittumiseen solussa, vaan merkitsevästi estävät PTENin fosfataasiaktiivisuuden ja sen takia moduloivat sen kykyä säädellä PI3K-signaalinjohtumis- kaskadia.

Ja toisaalta jos RNAinterferenssillä TRIM27 (RFP):n suhteen poistogeeniseksi tehty solu näyttää lisäävän PTENin fosfataasiaktiivisuutta ja sen vaimentavaa vaikutusta AKT-aktivaatioon. Lisäksi TRIM27- eli RFP-välitteinen PTEN-ubikitinaatio estää PTEN:istä riippuvaisen TRAIL-ilmenemän aktivaation ja myös vaimentaa sen kyvyn indusoida apoptoosia. Nämä tutkimukset osoittavat, miten keskeisen tärkeä osuus on TRIM27- väliteisellä PTEN-ubikitinaatiolla PTEN:in aktivaation kontrolloimisessa.

• The PTEN tumor suppressor is a lipid phosphatase that has a central role in regulating the phosphatidylinositol-3-kinase (PI3K) signal transduction cascade. Nevertheless, the mechanism by which the PTEN activity is regulated in cells needs further elucidation. Although previous studies have shown that ubiquitination of PTEN can modulate its stability and subcellular localization, the role of ubiquitination in the most critical aspect of PTEN function, its phosphatase activity, has not been fully addressed. Here, we identify a novel E3 ubiquitin ligase of PTEN, Ret finger protein (RFP), that is able to promote atypical polyubiquitinations of PTEN. These ubiquitinations do not lead to PTEN instability or relocalization, but rather significantly inhibit PTEN phosphatase activity and therefore modulate its ability to regulate the PI3K signal transduction cascade. Indeed, RFP overexpression relieves PTEN-mediated inhibitory effects on AKT activation; in contrast, RNAi-mediated knockdown of endogenous RFP enhances the ability of PTEN to suppress AKT activation. Moreover, RFP-mediated ubiquitination of PTEN inhibits PTEN-dependent activation of TRAIL expression and also suppresses its ability to induce apoptosis. Our findings demonstrate a crucial role of RFP-mediated ubiquitination in controlling PTEN activity.
  

6. These findings provide a cellular and molecular function for MAGE-L2-TRIM27 in retrograde transport, including an unappreciated role of K63-linked ubiquitination and identification of an activating signal of the WASH regulatory complex.
7. Data conclude that TRIM27 negatively regulates NOD2-mediated signaling by degradation of NOD2 and suggest that TRIM27 could be a new target for therapeutic intervention in NOD2-associated diseases.
8. TRIM27 expression is a modifier of cancer incidence and progression and is a potential target for intervention.
   

 

4.4. 2018