Tripartite motif-containing 14 is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
encoded by the TRIM14 gene in the
human genome
The human genome is a complete set of nucleic acid sequences for humans, encoded as DNA within the 23 chromosome pairs in cell nuclei and in a small DNA molecule found within individual mitochondria. These are usually treated separately as the n ...
. It belongs to the TRIM family of proteins which contain the TRIM motif on the N-terminus. TRIM14 lacks the RING domain within the motif and therefore it loses the function of E3 ubiquitin ligase in eukaryotic cells. Instead, the PRYSPRY domain on the C-terminus allows TRIM14 to be categorized into an evolutionarily younger group of TRIM proteins which are involved in the regulation of innate immunity. TRIM 14 is localized in both the
cytoplasm
In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The ...
and the
cell nucleus
The cell nucleus (pl. nuclei; from Latin or , meaning ''kernel'' or ''seed'') is a membrane-bound organelle found in eukaryotic cells. Eukaryotic cells usually have a single nucleus, but a few cell types, such as mammalian red blood cells, h ...
.
Function
TRIM14 acts in cell proliferation, differentiation, morphogenesis, autophagy and in the initiation of the anti-viral immune response by innate immunity.
Overexpression of TRIM14 in mouse embryonic stem cells (mESC) leads to upregulation of several genes (hsp90ab1, prr13, pu.1, tnfrsf13c (baff-r), tnfrsf13b (taci), hlx1, hbp1, junb and pdgfrb) which are involved in early stage differentiation of embryonic stem cells, in the mesodermal layer. The same genes are upregulated in human embryonic kidney cells 293 (HEK293) (except for hlx1, hbp1, junb and pdgfrb). Therefore, TRIM14 regulates gene expression in different cell types by a universal mechanism: interaction with the transcription factors common to TRIM proteins.
The mouse homologue of TRIM14, the "Pub protein", was shown to interact with transcription factor PU.1 (SPI1) and inhibit its activity. PU.1 is a transcription factor critical for proliferation and differentiation of myeloid cells and B lymphocytes. Hence, TRIM14 (Pub) is likely associated with the regulation of development of the immune cells.
TRIM14 transfected HEK293 cell show increased transcription of eighteen genes involved in the innate immune system. They are ifna, il6 (ifnb2), isg15, raf-1, NF-kB (nf-kb1, rela, nf-kb2, relb), grb2, grb3-3, traf3ip2, junB, c-myb, pu.1, akt1, tyk2, erk2, and mek2. In the same cells, the stable expression of TRIM14 allowed the suppression of the replication of
Sindbis virus
''Sindbis virus'' (SINV) is a member of the ''Togaviridae'' family, in the ''Alphavirus'' genus. The virus was first isolated in 1952 in Cairo, Egypt. The virus is transmitted by mosquitoes (''Culex'' and Culiseta). SINV is linked to Pogosta di ...
.
The influence of TRIM14 on RNA viruses replication was proven in several experiments
and it was found to be upregulated in viral-infected tissues.
Additionally, TRIM14 knockout mice are lethal after herpes simplex virus (HSV) infection.
The antiviral role of TRIM14 has also been confirmed by the inhibition of the selective autophagic degradation of the cytoplasmic DNA sensor, cGAS. In normal cells, cGAS is modified by the K48-polyubiquitin chain. It goes to the p62 mediated autophagic degradation and the type I IFN signalling is suppressed. Induction of TRIM14 by type I IFN leads to activation of USP14 which then cleaves the polyubiquitin chain from cGAS and type I IFN signalling is stabilized. So, there is a positive loop between TRIM14 and type I IFN signalling.
Expression pattern
The mRNA for TRIM14 has been found in many organs with a prevalence in those organs with a high number of immune cells such as the spleen, lymph nodes, and gastrointestinal tract.
[{{Cite web, url=http://www.proteinatlas.org/ENSG00000106785-TRIM14/tissue, title=Tissue expression of TRIM14 - Summary - The Human Protein Atlas, website=www.proteinatlas.org, access-date=2017-01-27]
References
Human genes
Human proteins