https://www.ncbi.nlm.nih.gov/protein/NP_055603.2
Aminohappojärjestyksessä on 442 aminohappoa. , siis TRIMproteiiniksi keskikokoinen,
Sen jaksossa 269..441 on havaittu PRY SPRY motiivia.
Artikkeletia on kohtalaisen paljon, ja koska TRIM14 osuus, joko sen puuttuminen tai yliesiintymä noin strategisessa kohdassa on kiinnostava asia, ottaen huomioon RNA-virusten invaasion määrän ihmiskehoa vastaan, otan erikseen niistä sitaatteja.
TRIM14-omaa taustasäätömolekyylin Se on TRAC1 (TNORS) eli RNF125 RING-fingerproteiini kromosomista 18. Se on T-solun RING-proteiini ja sitä ilmenee eniten lymfoidisessa kudoksessa, luuytimessä, pernassa ja kateenkorvassa. Se ubikitinoi TRIM14 molekyylin lysiini48 kohtaan ja johtaa sen proteosomisilppuriin. Tämä moduloi vahvasti solun antivirusvasteen suuntautumista. Katso allaoleva kartta. Siinä heikkenee RIG-1-MAVS-NEMO-akseli, jossaTRIM on NEMOa rekrytoiva molekyyli, joten TRAC-1 eli RNF125 moduloi luonnollista immuunivastetat merkitsevästi.
- Enhanced expression of trim14 gene suppressed Sindbis virus reproduction and modulated the transcription of a large number of genes of innate immunity. Nenasheva VV, et al. Immunol Res, 2015 Jul. PMID 25948474 (Suom. Sindbis virus SINV on alphavius, TOGA viruksia , ja TRIM14 pystyi vaimentamaan sen tuotantoa luonnollisen immuniteetin kautta.
- Bispecific antibody suppresses osteosarcoma aggressiveness through regulation of NF-κB signaling pathway. Yu GH, et al. Tumour Biol, 2017 Jun. PMID 2863155 (Suom osteosarkoomakudoksessa TRIM on säätynyt ylös tässä luusyövässä ja edistää osteosarkoomasolujen alkuvaihetta, progredioitumista , angiogeneesiä, invaasiota ja apoptoosireseitenssiä cisplatiinia vastaan. Bmi-1 ja TRIM14 aiheuttivat NFkB:n translokoitumisen tumaan luusyöpäsoluissa. iitä vastaan on tehty bispesifinen vasta-aine: BsAbBmi/TRIM. ne estivät MMP9 promoottoriperäistä NFkB ilmenemää merkitsevästi.
- Osteosarcoma is one of the most lethal malignancies, and the prognosis remains dismal due to the paucity of effective therapeutic targets. Bmi-1 and TRIM-14 are associated with the initiation and progression of osteosarcoma, which could promote angiogenesis, invasion, and apoptotic resistance in bone cancer tissue. In this study, we constructed a bispecific antibody of BsAbBmi/TRIM targeting Bmi-1 and TRIM-14 and investigated the therapeutic value in bone carcinoma cells and xenograft mice. Our results showed that Bmi-1 and TRIM-14 expression levels were markedly upregulated correlated with nuclear factor-κB nuclear translocation in bone cancer cells and clinical carcinoma tissues. Results have demonstrated that overexpression of Bmi-1 and TRIM-14 promoted growth, proliferation, aggressiveness, and apoptosis resistance of osteosarcoma cells. BsAbBmi/TRIM administration significantly inhibited nuclear factor-κB expression derived by matrix metalloproteinase-9 promoter. BsAbBmi/TRIM administration inhibited growth of osteosarcoma cells and downregulated Bmi-1 and TRIM-14 expression levels. Data also demonstrated that migration and invasion of osteosarcoma cells were also inhibited by BsAbBmi/TRIM. In addition, results illustrated that BsAbBmi/TRIM inhibited tumor growth and tumorigenicity by blockaded sensor expression in nuclear factor-κB signal pathway. Furthermore, in vivo study showed that BsAbBmi/TRIM treatment markedly inhibited the tumorigenicity and growth of osteosarcoma cells compared to either AbBmi-1 or AbTRIM-14 treatment. Notably, survival of xenograft mice was prolonged by BsAbBmi/TRIM treatment compared to either AbBmi-1 or AbTRIM-14 treatment. In conclusion, these results provided new evidence that BsAbBmi/TRIM inhibited the progression of osteosarcoma, which suggest that BsAbBmi/TRIM may be a novel anti-cancer agent for osteosarcoma therapy.
- miR-15b inhibits cancer-initiating cell phenotypes and chemoresistance of cisplatin by targeting TRIM14 in oral tongue squamous cell cancer. Wang X, et al. Oncol Rep, 2017 May. PMID 28350138 (Suomennosta) Syöpäkudoksessa ilmenevä TRIM14 aiheutti syöpää aloittavia soluja ja epiteliaalisesta mesenkymaaliseksi transitiota (EMT) , mutta sitävastoin mikroRNA miR-15b esti syöpäsolufenotyyppiä ja päinvastoin edisti mesenkymaalisesta epiteliaaliseksi transitiota (MET) ja herkisti cisplatiinille siis palautti kemoresistenssiä.
- In the present study, we showed that TRIM14 induced formation of cancer-initiating cells and EMT in TSCC SCC25 cells. Its overexpression promoted cisplatin resistance in the SCC25 cells. We found that overexpression of miR-15b suppressed TRIM14 and inhibited CIC phenotypes in the SCC25 cells. Moreover, overexpression of miR-15b promoted mesenchymal-epithelial transition (MET) in the SCC25 cells and sensitized cisplatin-resistant SCC25 (SCC25-res) cells to cisplatin. Thus, we conclude that miR-15b inhibited cancer stem cell phenotypes and its restoration reversed the chemoresistance of cisplatin by targeting TRIM14 in TSCC. Elucidating the molecular mechanism of EMT and cancer stem cells in TSCC may further aid in the understanding of the pathogenesis and progression of the disease, and offer novel targets for the discovery of new drugs.
- Overexpression of TRIM14 promotes tongue squamous cell carcinoma aggressiveness by activating the NF-κB signaling pathway. Su X, et al. Oncotarget, 2016 Mar 1. PMID 26799420, Free PMC Article (Suomennosta) Suuontelon levyepiteelikarsinoma on säätänyt ylös TRIM14 syöpåsoluissa ja sen ilmenemä korreloi syövän TNM luokitukseen. TRIM14 ektooppinen ilmenemä näissä syöpäsoluissa edisti proliferaatiota, angiogeneesiä ja lisääntynyttä resistenssiä cisplatiinin indusoimaa apotoosia kohtaan . TRIM14 yliilmenemä lisäsi syöpäsolujen tumorigeenisyyttä ja endogeenisen TRIM14:ta hiljentäminen taas vaikutti päinvastoin. TRIM14 lisäsi syövän aggressiivisuutta aktivoimalla NF-kB-signaloinnin. TRIM14 yliesiintymä saataa olla uusi terapian kohde.
- Tongue squamous cells carcinoma (TSCC) is one of the most lethal malignancies of oral cancers and its prognosis remains dismal due to the paucity of effective therapeutic targets. Herein, we showed that Tripartite motif containing 14(TRIM14) is markedly up-regulated in TSCC cell lines and clinical tissues. Immunohistochemical (IHC) analysis of 116 clinical TSCC specimens revealed that TRIM14 expression was significantly correlated with the TNM classification (T: P = 0.01; N: P < 0.001; M: P < 0.001) in patients with TSCC. Multivariate analysis indicated that TRIM14 expression might be an independent prognostic indicator for the survival of patients with TSCC. Ectopic expression of TRIM14 in TSCC cells promoted proliferation, angiogenesis, and increased resistance to cisplatin-induced apoptosis of TSCC cells in vitro. Furthermore, TRIM14 overexpressing significantly promoted the tumorigenicity of TSCC cells in vivo whereas silencing endogenous TRIM14 caused an opposite outcome. Moreover, we demonstrated that TRIM14 enhanced TSCC aggressiveness by activating NF-κB signaling. Together, our results provide new evidence that TRIM14 overexpression promotes the progression of TSCC and might represent a novel therapeutic target for its treatment.
- Assembly of the WHIP-TRIM14-PPP6C Mitochondrial Complex Promotes RIG-I-Mediated Antiviral Signaling. Tan P, et al. Mol Cell, 2017 Oct 19. PMID 29053956 (Suomennosta) Mitokondriaalisen antivirussignaloinnin alustaproteiini MAVS on keskipiste virusta havaitsevan RIG-1 reseptorisignaloinnin alkuetenemisessä . Vielä 2017 katsotaan RIG-1:tä mitokondriaan päin lokalisoivan mitokondriaalisen tapahtuma-alustan (MAVS) avainkomponenttien kokoontuminen ja optimaalinen aktivaatio suurelta osin definioimattomiksi asioiksi . Tutkijat raportoivat TRIM14:n olevan mitokondriaalinen adaptoriproteiini, joka tarjoaa mitokondriaalisen signaloinnin kompleksin koostumalle alustaa, joka on tärkeää RIG-1 väliteisen signaloinnin maksimaaliselle aktivoitumiselle. ja siihen kuuluu WHIP ja proteiinifosfataasi PPP6C. Kun on tapahtunut virusinfektio ubikitiiiä sitova domeeni WHIP tekee siltaa RIG-1 ja MAVS:n kesken sitoutumalla RIG-1 K164 :n polyubikitiiniin. WHIP:n ATPaasi domaani vaikutta osaltaan stabiloiden RIG-1/dsRNA interaktiota. Fosfataasin osuus on RIG-1:n defosforylaatio. Tässä osoitetaan WHIP-TRIM14-PPP6C mitokondriaalinen signalosomi tarvittavaksi RIG-1 välitteisessä luonnollisessa antivirusimmuniteetissa . selventävä KUVA on alla olevass linkissä.
- Mitochondrial antiviral signaling platform protein (MAVS) acts as a central hub for RIG-I receptor proximal signal propagation. However, key components in the assembly of the MAVS mitochondrial platform that promote RIG-I mitochondrial localization and optimal activation are still largely undefined. Employing pooled RNAi and yeast two-hybrid screenings, we report that the mitochondrial adaptor protein tripartite motif (TRIM)14 provides a docking platform for the assembly of the mitochondrial signaling complex required for maximal activation of RIG-I-mediated signaling, consisting of WHIP and protein phosphatase PPP6C. Following viral infection, the ubiquitin-binding domain in WHIP bridges RIG-I with MAVS by binding to polyUb chains of RIG-I at lysine 164. The ATPase domain in WHIP contributes to stabilization of the RIG-I-dsRNA interaction. Moreover, phosphatase PPP6C is responsible for RIG-I dephosphorylation. Together, our findings define the WHIP-TRIM14-PPP6C mitochondrial signalosome required for RIG-I-mediated innate antiviral immunity.
- http://www.cell.com/molecular-cell/abstract/S1097-2765(17)30713-Xhttp://www.cell.com/molecular-cell/abstract/S1097-2765(17)30713-X
GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?
- findings define the WHIP-TRIM14-PPP6C mitochondrial signalosome required for RIG-I-mediated innate antiviral immunity.
- study identifies new gene-type zinc finger protein 125 (RNF125) as a negative regulator of TRIM14 in the innate antiviral immune response
- http://www.jimmunol.org/content/174/9/5288
- survival of xenograft mice was prolonged by BsAbBmi/TRIM treatment compared to either AbBmi-1 or AbTRIM-14 treatment. In conclusion, these results provided new evidence that BsAbBmi/TRIM inhibited the progression of osteosarcoma, which suggest that BsAbBmi/TRIM may be a novel anti-cancer agent for osteosarcoma therapy
- MiR-15b degrades TRIM14 in oral tongue squamous cell cancer.TRIM14 role in oral tongue squamous cell cancer resistance to cisplatin.
- Data suggest that tripartite motif containing 14 protein (TRIM14) might play an important role in the malignant progression of tongue squamous cells carcinoma (TSCC) and in regulation of the NF_Kappa B (NF-kappaB) signaling pathway.
- stable enhanced expression of trim14 gene in cells activates the transcription of many immunity genes and suppresses Sindbis virus reproduction, but Sindbis virus infection of HEK-trim14 cells promotes inhibition of some genes involved in innate immunity.
- Upon virus infection, TRIM14 recruits NF-kappaB essential modulator (NEMO) to the MAVS complex via ubiquitin chains.
- Observational study of gene-disease association. (HuGE Navigator)
Inga kommentarer:
Skicka en kommentar