Disease relevance of TARBP2

• TRBP and PKR are involved in the regulation of HIV-1 gene expression through their binding to TAR RNA [1].
• The poor translation of HIV-1 mRNA and consequent limited virion production can be restored by overexpression of TRBP proteins in the astrocytoma U251MG cells [2].
• TRBP could contribute to improved HIV expression in murine models [3].
• In contrast, other inhibitors of PKR including vaccinia virus E3L and K3L gene products, and the HIV trans-activating response (TAR) element binding protein TRBP, did not disrupt ribosome association of PKR [4].
• A previously characterized DNA binding activity called terminal repeat or tandem repeat binding protein (TRBP) was found to recognize several G-rich recombinogenic sequences in the EBV genome and in cellular DNA [5].

High impact information on TARBP2

• Here we show that RISC is composed of Dicer, the double-stranded RNA binding protein TRBP, and Argonaute2 [6].
• In intracellular and in cell-free assays we show that TRBP directly inhibits PKR autophosphorylation through an RNA binding-independent pathway [7].
• Biologically, TRBP serves a growth-promoting role; cells that overexpress TRBP exhibit transformed phenotypes [7].
• Our results demonstrate the oncogenic potential of TRBP and are consistent with the notion that intracellular PKR function contributes physiologically towards regulating cellular proliferation [7].
• In transfection assays, TRBP has also been shown to inhibit the interferon-induced protein kinase PKR possibly by direct physical interaction [8].

Biological context of TARBP2

• Cells overexpressing TRBP showed enhanced cell growth in cell proliferation assays and also exhibited transformed phenotypes, such as anchorage-independent cell growth and tumor development in mouse xenografts [9].
• These domains are conserved with the cis-acting transactivation response element (TAR)-binding protein (TRBP) and dsRNA-activated protein kinase (PKR) [1].
• The absence of full alignment between TRBP2 full-length cDNA and this sequence suggests that the stem-loop structure could have prevented a complete reverse transcription during pseudogene formation [3].
• Using different antibodies, three forms of TRBP can be identified in primate cells at 40, 43 and 50 kD, suggesting a differential expression from the cDNAs and post-translational modifications [3].
• We have also isolated the DNA sequence that represents the TRBP processed pseudogene [3].

Anatomical context of TARBP2

• Endogenous expression is restricted in astrocytes due to limited TRBP promoter expression compared to lymphocytes [2].
• An NF-YA trans-dominant mutant decreased TRBP1 promoter expression fourfold in Jurkat cells, thus demonstrating the functional importance of NF-Y factors in lymphocytes [2].
• Immunoprecipitation of TRBP from human immunodeficiency virus type 1-infected T lymphocytes recovered TAR RNA [10].
• This minimal TRBP promoter activity may account for minimal HIV-1 replication in astrocytes [11].
• Organization of the human tarbp2 gene reveals two promoters that are repressed in an astrocytic cell line [11].

Associations of TARBP2 with chemical compounds

• Merlin efficiently inhibited these oncogenic activities of TRBP in our experiments [9].

Physical interactions of TARBP2

• We characterized two independent PKR-binding sites in TRBP [12].
• In this work, we describe the identification of TRBP (human immunodeficiency virus (HIV-1) transactivating response (TAR) RNA-binding protein) as a protein partner of human Dicer [13].

Regulatory relationships of TARBP2

• These data suggest that TRBP activates gene expression in PKR-dependent and PKR-independent manners [12].
• These results are in agreement with the probable role of TRBP in the control of human protamine mRNA translation [14].
• In this report, we investigated how merlin inhibits the oncogenic activity of TRBP in association with cell growth conditions [15].

Other interactions of TARBP2

• The expression of both CycT1 and TRBP2 had a more than additive activity on RT function in cell extracts and on viral particle production in supernatant of murine cells [16].
• TRBP promoters are TATA-less but have CCAAT boxes, a CpG island, and several potential binding sites for transcriptional factors [11].
• TAR RNA-binding protein, TRBP, was recently discovered to be an essential partner for Dicer and a crucial component of the RNA-induced silencing complex (RISC), a critical element of the RNA interference (RNAi) of the cell apparatus [17].
• In the human embryonic kidney 293 cell line, the level of endogenous merlin increased, whereas that of endogenous TRBP significantly decreased along with the increase in cell confluence [15].

Analytical, diagnostic and therapeutic context of TARBP2

• Western blotting indicates that despite high sequence conservation in human and mouse, the TARBP2 protein differs in apparent size in primate and rodent cells [18].
• The interaction between TRBP and merlin was confirmed by glutathione S-transferase pull-down assays, co-immunoprecipitation, and co-localization experiments [9].
• By PCR amplification of a human library, we have isolated an additional 22 nucleotides in the 5' end of TRBP2 cDNA [3].
• At the ultrastructural level, quantitative analysis of both TRBP mRNA and protein, using electron microscopy in-situ hybridization and immunocytochemistry, showed that TRBP is expressed mainly in spermatids at steps 3-4 of spermiogenesis [14].
• Xlrbpa and human TRBP can be detected in the cytoplasm and nucleus by immunofluorescence staining and Western blotting [8].

References