{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T02:02:48Z","timestamp":1784340168684,"version":"3.55.0"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>l-asparaginase (l-ASP) is an important chemotherapeutic agent used in the treatment of pediatric acute lymphoblastic leukemia (ALL). However, resistance to l-ASP is an unfavorable prognostic factor, and the mechanism underlying l-ASP resistance is not fully understood. Here, we show that activation of the activating transcription factor 4 (ATF4) and induced expression of downstream target asparagine synthetase (ASNS) play a pivotal role in l-ASP resistance of ALL cells. In addition, the G protein pathway suppressor 2 (GPS2) binds to ATF4 and stabilizes ATF4 protein. Mechanistically, GPS2 inhibits ubiquitin-proteasome degradation of ATF4 through impairing the interaction between ATF4 and beta-transducin repeat-containing E3 ubiquitin protein ligase (BTRC), an E3 ligase that triggers proteasomal degradation of ATF4. Moreover, GPS2 knockdown sensitizes ALL cells to l-ASP treatment via repressing the ATF4\/ASNS axis in vitro and increases l-ASP efficacy against xenografted ALL tumors in vivo. Taken together, these findings demonstrate that GPS2 positively regulates the ATF4\/ASNS axis to confer l-ASP resistance in ALL cells, suggesting a therapeutic potential of targeting this pathway to overcome l-ASP resistance.<\/jats:p>","DOI":"10.1093\/carcin\/bgaf035","type":"journal-article","created":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T08:56:40Z","timestamp":1753174600000},"source":"Crossref","is-referenced-by-count":4,"title":["GPS2 confers <scp>l<\/scp>-asparaginase resistance in acute lymphoblastic leukemia cells through ATF4\/ASNS axis"],"prefix":"10.1093","volume":"46","author":[{"given":"Jie","family":"Chen","sequence":"first","affiliation":[{"name":"Cancer Center, Medical Research Institute, Southwest University , Chongqing 400715 ,","place":["China"]},{"name":"Jinfeng Laboratory , Chongqing 401329 ,","place":["China"]},{"name":"Engineering Research Center for Cancer Biomedical and Translational Medicine, Southwest University , Chongqing 400715 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