Involvement of ribosomal protein L11 expression in sensitivity of gastric cancer against 5-FU.

5-Fluorouracil (5-FU) is widely used in the treatment of various types of solid cancer. Our study showed that ribosomal protein L11 (RPL11) was a crucial factor affecting sensitivity of gastric cancer to 5-FU, implying that RPL11 expression is a potential biomarker for predicting 5-FU sensitivity. Kaplan-Meier survival analysis indicated that high RPL11 expression in gastric cancer patients treated with 5-FU was significantly associated with good prognosis. It was therefore investigated whether RPL11 affected the sensitivity of gastric cancer against 5-FU using four human gastric cancer cell lines, MKN45 (wild-type TP53 gene), NUGC4 (wild-type), MKN7 (mutated), and KE39 cells (mutated). In vitro assays demonstrated that RPL11 knockdown in gastric cancer cell lines carrying the TP53 wild-type gene attenuated 5-FU-induced cell growth suppression and activation of the P53 pathway, but not in cells carrying mutated TP53, suggesting that 5-FU suppresses tumor progression via RPL11-mediated activation of the P53 pathway in gastric cancer. The present study provides a potential therapeutic strategy for improving 5-FU resistance in gastric cancer by elevating RPL11 expression.

Serotriflin, a CRISP family protein with binding affinity for small serum protein-2 in snake serum.

Habu (Trimeresurus flavoviridis) serum contains 3 small serum proteins (SSP-1, SSP-2, and SSP-3) with molecular masses of 6.5 to 10 kDa. Gel filtration analysis showed that all the SSPs exist in high molecular mass forms of approximately 60 kDa in the serum. Ultrafiltration of Habu serum showed that SSPs dissociated from the complex below a pH of 4. An SSP-binding protein was purified from Habu serum by gel filtration, ion exchange, and reverse-phase HPLC. N-terminal sequencing yielded a 39-amino acid sequence, similar to the N-terminal region of triflin, which is a snake venom-derived Ca2+ channel blocker that suppresses smooth muscle contraction. The amino acid sequence of this protein, termed serotriflin, was established by peptide analysis and cDNA cloning. Serotriflin is a glycosylated protein and consists of 221 amino acids. Among the 3 SSPs, only SSP-2 formed a noncovalent complex with serotriflin. It was bound to triflin and serotriflin with high affinity, as evidenced by surface plasmon resonance. SSP-2 is considered to be a protein that prevents self injury by accidental leaking of venom into the blood.

Identification of novel serum proteins in a Japanese viper: homologs of mammalian PSP94.

Three small serum proteins (SSP-1, -2, and -3), with molecular masses of 6.5-10kDa, were isolated from Habu (Trimeresurus flavoviridis) serum, and the amino acid sequences were determined by protein and cDNA analysis. Despite only limited sequence identity to any mammalian prostatic secretory protein of 94 amino acids (PSP94), all of the Cys residues in these SSPs were well conserved. SSPs are the first PSP94 family proteins to be identified in reptiles. SSP-1 and -3 weakly inhibited the proteolytic activity of a snake venom metalloproteinase. On the other hand, SSP-2 formed a tight complex with triflin, a snake venom-derived Ca(2+) channel blocker that suppresses the smooth muscle contraction. This suggests a role for SSP-2 in the self defense system of venomous snakes.