Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

Objective To study the HPLC fingerprints of isoflavones from different medicinal plants of G.max and establish a sensitive and specific method for controlling the quality of the soybean isoflavone.Methods The gradient elution mode was applied in chromatographic separation.A C_(18) column(250 mm?4.6 mm,5 ?m) was used with the mobile phase: ice acetic acid water solution(pH value 3.2)-methanol,flow rate: 0.6 mL/min,detecting wavelength: 261 nm,and the column temperature: room temperature.All 25 samples collected from different species were determined.The clustering analysis and the software of similarity analysis were applied for datum analysis.Results This method had a good repeatability and reproducibility.The ratio of peaks′ area from distinct samples were different.Conclusion The method can show the difference of chemical compositions among species completely and can be used as a quality control method for soybean.

Objective To establish a method for the quality control of Rhizoma Alismatis. Methods The samples of Rhizoma Alismatis were identified with TLC and the content of alisol B-23-acetate in Rhizoma Alismatis was determined by HPLC-ELSD. Results The spots of TLC chromatogram of Rhizoma Alismatis was clear. A good linearity was in the range of 4.4～110.0 ?g/mL of alisol B-23-acetate, r=0.999 2(n=5), and the average recovery rate was 98.98 %(n=9), RSD=1.3 %. Conclusion This method was simple, accurate and with a good reproducibility and can be used for the quality control of Rhizoma Alismatis.