Increased Expression of Queuosine Synthesizing Enzyme, tRNA-Guanine Transglycosylase, and Queuosine Levels in tRNA of Leukemic Cells

Abstract

Queuosine is a modified nucleoside located at the first position of the tRNA anticodon, which is synthesized by tRNA-guanine transglycosylase (TGT). Although the levels of queuosine in cancer cells have been reported to be lower than those in normal cells, the expression levels of TGT remain to be determined. We determined the expression levels of a subunit of TGT (TGT60KD). Contrary of our expectations, the results revealed higher levels of expression of TGT60KD than that in normal cells, and the level of queuosine in the tRNA fraction corresponded with that of TGT60KD expression. These results suggest the possibilities that the expression levels of TGT60KD regulate TGT activity and the levels of queuosine, and that TGT60KD plays significant roles in carcinogenesis. To our knowledge, this is a first report of increased expression levels of TGT60KD in human cancer cells.

Over-Expression of Deubiquitinating Enzyme USP14 in Lung Adenocarcinoma Promotes Proliferation through the Accumulation of β-Catenin

“…To date, only a few studies have implicated USP14 in cancer [15–17], and to the best of our knowledge, this is perhaps the first report demonstrating the role of USP14 in lung adenocarcinoma. Previous studies showed that USP14 protein and mRNA levels were dysregulated in patients with more aggressive tumors of leukemia, colon cancer, and intrahepatic cholangiocarcinoma [15–17].…”

“…Previous studies showed that USP14 protein and mRNA levels were dysregulated in patients with more aggressive tumors of leukemia, colon cancer, and intrahepatic cholangiocarcinoma [15–17]. These papers are very important because they provide evidence that USP14 is implicated in cancer biology.…”

“…To date, only a few studies have implicated USP14 in cancer. Ishiwata, et al , first found that the USP14 expression was upregulated in leukemic cells in 2001 [15], Shinji et al , found that the USP14 expression in colorectal cancer is associated with liver and lymph node metastases in 2006, and Chuensumran, et al , found that USP14 expression is associated with intrahepatic cholangiocarcinoma cell differentiation in 2011 [16,17]. However, to the best of our knowledge, there is as yet no report demonstrating a role for USP14 in lung adenocarcinoma.…”

Crystal structure of S‐adenosylmethionine:tRNA ribosyltransferase‐isomerase (QueA) from Thermotoga maritima at 2.0 Å resolution reveals a new fold

“…Queuine functions as a growth modulator for higher eukaryotes that significantly reduces overall protein synthesis in mammalian cells, and modulates the phosphorylation of specific proteins 4. Queuine deficiency has been observed in tRNAs from ovarian tumors,5 whereas increased levels of Q have been observed in human leukemic cells 6. Here, we report the crystal structure of TM0574, that was determined using the semiautomated, high‐throughput pipeline of the Joint Center for Structural Genomics (JCSG) 7…”

Turning tRNA upside down: When aminoacylation is not a prerequisite to protein synthesis

“…Along these lines, mutants in Q-base synthesis in Shigella have been shown to exhibit reduced virulence, a phenotype associated with reduced translation of the virulence factor VirF (14). This phenotype is akin to the requirements for Q-base synthesis in some cancerous cells (15), a fact that was recognized early on. In any event, final assignment of the function of this modification will ultimately require settling the question of whether YadBmediated glutamylation extends to other Q-base-containing tRNAs, such as tRNA His and tRNA Tyr .…”