TRIM26 (Kr.6p21.3), AFP, RNF95, ZNF173 (Alaryhmä C IV, PRY/SPRY)
TRIM26 on havaittu 1995 aikaan ja eräs sen nimistä on ”acidic finger protein”, AFP. Kun se oli kloonattu sinkkisormiproteiinina, sen nimi oli ZNF173 . Nykyään se on C IV alaluokan TRIM proteiini: Siis siinä on RING domeeni, B-box1 ja B-Box2 sekä helikaalinen C-C (coiled coil) alue ja C-terminaalissa PRY/SPRY. Sen erityistä funktiota on etsitty. Ainakin on havaittu RING-domeenin pystyvän sitomaan DNA:ta. Geeni sijoittautuu MHC-I-luokan geenien alueeseen kromosomissa 6. Eniten tätä geeniä ilmenee munuaisessa ja pernassa ja myös 25 muussa kudoksessa. Maksasolusyövässä tällä TRIM26-geenillä on tuumorisuppressiivinen vaikutus ja geenin alassäätyminen on prognostisesti huono merkki. Tietoa voitaneen hyödyntää maksasyöpäterapiassa. TRIM26 osallistuu myös luonnolliseen immuniteettiin liittymässä solussa interferonin eritykselle kriittiseen TBK1 kinaasiin. Jos RNA-virusta tulee soluun (RIG-1 kaltaiset reseptorit tunnistavat sen), TRIM26 autoubikitinoituu ja ilmeisesti myös TBK1 saa ubikitinaatiosta posttranslationaalisen osansa ja kompleksi liittyy NEMO:oon ja vetäytyy mitokondrian MAVS-proteiinien yhteyteen, jolloin TBK1 aktivoituu ja fosforyloi IRF3:n interferonin tuotantoon johtavassa ketjussa. (MAVS = mitokondriaalinen antiviraali signaloiva proteiini) (NEMO = NFkB essential modulator; IKKgamma, kBkinaasin inhibiittori) Tässä yhteydessä otan erikseen lisätietoa NF-kB- säätelystä ubikitinaatiolla.-
https://www.ncbi.nlm.nih.gov/gene/7726
, TRIM26 Gene, AFP; RNF95; ZNF173
-
Summary. The protein encoded by this gene is 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. The protein localizes to cytoplasmic bodies.
Although the function of the protein is unknown, the RING domain
suggests that the protein may have DNA-binding activity. The gene
localizes to the major histocompatibility complex (MHC) class I
region on chromosome 6. Alternatively spliced transcript variants
encoding the same protein have been found for this gene. [provided
by RefSeq, Jun 2011] Expression Ubiquitous expression in kidney
(RPKM 14.9), spleen (RPKM 12.6) and 25 other tissues See
more
-
https://www.ncbi.nlm.nih.gov/gene/7726#gene-expression
AFP ( Acidic Finger protein) ; RNF95; ZNF173 Summary .The protein
encoded by this gene is 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. The
protein localizes to cytoplasmic bodies. Although the function of
the protein is unknown, the RING domain suggests that the protein
may have DNA-binding activity. The gene localizes to the major
histocompatibility complex (MHC) class I region on chromosome 6.
Alternatively spliced transcript variants encoding the same protein
have been found for this gene. [provided by RefSeq, Jun 2011]
Related articles in PubMed
-
TRIM26 functions as a novel tumor suppressor of hepatocellular carcinoma and its downregulation contributes to worse prognosis. Wang Y, et al. Biochem Biophys Res Commun, 2015 Jul 31. PMID 26043685 Hepatocellular carcinoma (HCC) is the one of the most common malignancies worldwide and its prognosis is extremely poor. Tripartite motif (TRIM) proteins play crucial roles in cancer cell biology but the function of tripartite motif 26 (TRIM26) has not been investigated. We demonstrated that low expression level of TRIM26 in tumor samples was significantly correlated with worse prognosis in HCC patients. We also demonstrated its expression level was associated with several clinicopathologic features such as AFP level and T stage of HCC patients. Furthermore, we validated that TRIM26 was significantly downregulated in HCC tissue compared with normal liver tissue. To further clarify the functional role of TRIM26 in HCC, We confirmed that TRIM26 silencing can promote cancer cell proliferation, colony forming, migration and invasion in vitro with HCC cell lines HepG2 and Bel-7402. Then we utilized bioinformatic tool to predict gene influenced by TRIM26, showing TRIM26 could modulate gene sets about cancer cell metabolism. In conclusion, we proved that TRIM26 is a novel tumor suppressor modulating multiple metabolism-related pathways in HCC. To our best knowledge, this is the first study to investigate the function of TRIM26 in cancer biology. Our findings provide useful insight into the mechanism of HCC origin and progression. Moreover, TRIM26 may represent a novel therapeutic target for HCC.
-
Association study between TRIM26 polymorphisms and risk of aspirin-exacerbated respiratory disease. Lee JS, et al. Int J Mol Med, 2012 May. PMID 22294275
-
Cloning of a new "finger" protein gene (ZNF173) within the class I region of the human MHC. Chu TW, et al. Genomics, 1995 Sep 1. PMID 8530076 Abstract The human major histocompatability complex contains genes of both immune and nonimmune importance. Recently, several genes encoding novel, non-HLA products have been described in this area. We have performed positional cloning of short fragment cDNA sequences from the class I region of the human MHC using a hybridization selection approach. This report describes isolation of full-length cDNA clones and partial genomic clones that encode a protein that contains two domains rich in cysteine and histidine similar to those characteristic of metal-dependent DNA binding proteins (C3HC4). The predicted protein also contains a domain thought to form a coiled-coil that may promote dimerization. A third feature is a polyglutamic acid region near the carboxyl terminus of the conceptual protein. Because of these properties, we have named this gene product acid finger protein (AFP). Although the biological role of AFP is unknown at present, one potential function is binding of nucleic acids. The gene (ZNF173) is expressed in multiple tissues and is conserved among mammals. In particular, the mouse and human coding regions are highly conserved. In addition to AFP, other related sequences have been localized to the MHC, suggesting that multiple AFP-like genes exist in this area.
-
Autoubiquitination
of TRIM26 links TBK1 to NEMO in RLR-mediated innate antiviral immune
response. Ran Y, et al. J Mol Cell Biol, 2016 Feb. PMID
26611359 The transcription factors IRF3 and NF-κB are required for
the expression of many genes involved in antiviral innate immune
response, including type I interferons (IFNs) and proinflammatory
cytokines. It is well established that TBK1 is an essential kinase
engaged downstream of multiple pattern-recognition receptors (PRRs)
to mediate IRF3 phosphorylation and activation, whereas the precise
mechanisms of TBK1 activation have not been fully elucidated yet.
Here, we identified tripartite motif 26 (TRIM26) as an important
regulator for RNA virus-triggered innate immune response. Knockdown
of TRIM26 impaired virus-triggered IRF3, NF-κB activation, IFN-β
induction, and cellular antiviral response. TRIM26 was physically
associated with TBK1 independent of viral infection. As an E3
ligase, TRIM26 underwent autoubiquitination upon viral infection.
Ubiquitinated TRIM26 subsequently associated with NEMO, thus
bridging TBK1-NEMO interaction, which is critical for the
recruitment of TBK1 to the VISA signalsome and activation of TBK1.
Our findings suggest that TRIM26 is an important regulator of innate
immune responses against RNA viruses, which functions by bridging
TBK1 to NEMO and mediating the activation of TBK1.
-
https://www.semanticscholar.org/paper/NEMO-Binds-Ubiquitinated-TANK-Binding-Kinase-1-to-Wang-Li/07512f845178231ecc32c5e8cd44cda4b4ebc4b7
RIG-I like receptors (RLR) are intracellular sensors utilized by
nearly all cell types for recognition of viral RNA, initiation of
antiviral defense, and induction of type I interferons (IFN). TBK1
is a critical kinase implicated in RLR-dependent IFN transcription.
Posttranslational modification of TBK1 by K63-linked ubiquitin is
required for RLR driven signaling. However, the TBK1 ubiquitin
acceptor sites and the function of ubiquitinated TBK1 in the
signaling cascade are unknown. We now show that TBK1 is
ubiquitinated on residues K69, K154, and K372 in response to
infection with RNA virus. The K69 and K154 residues are critical for
innate antiviral responses and IFN production. Ubiquitinated TBK1
recruits the downstream adaptor NEMO through ubiquitin binding
domains. The assembly of the NEMO/TBK1 complex on the
mitochondrial protein MAVS leads to activation of TBK1 kinase
activity and phosphorylation of the transcription factor, interferon
response factor 3. The combined results refine current views of RLR
signaling, define the role of TBK1 polyubiquitination, and detail
the mechanisms involved in signalosome assembly.
Päivitystä TRIM26, 4.4. 2018
Inga kommentarer:
Skicka en kommentar