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However, the role of the TRIM family in PAs is not well recognized.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>CRISPR screening explored the role of the TRIM family in cell proliferation and drug resistance in PAs. In vitro and in vivo experiments were performed to evaluate the effects of Tripartite Motif Containing 21 (TRIM21). RNA-sequencing, mass spectrometry, immunoprecipitation, and ubiquitination experiments were performed to explore the molecular mechanism. NanoBiT assays were used to screen the drugs reducing TRIM21 expression.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>CRISPR-Cas9 screens identified that TRIM21 facilitated cell proliferation and drug resistance in PAs. Mechanistically, TRIM21 interacted with ERK1\/2 through PRY-SPRY domain, leading to ERK1\/2 K27-linked ubiquitination. The ERK1\/2 ubiquitination promotes the interaction between ERK1\/2 and MEK1\/2, thereby facilitating the phosphorylation of ERK1\/2. However, an excess presence of TRIM21 suppressed the phosphorylation of ERK1\/2 and cell proliferation via activating ERK1\/2 negative feedback pathways. Importantly, TRIM21 was upregulated in dopamine-resistant prolactinomas and cabergoline-resistant MMQ cells. Furthermore, drug screening identified that Fimepinostat and Quisinostat, can reduce the protein levels of TRIM21, inhibit tumor progression, and increase drug sensitivity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>TRIM21 may represent a therapeutic target for tumors, and inhibiting TRIM21 could be a potential strategy for tumor treatment.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/neuonc\/noae241","type":"journal-article","created":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T10:51:06Z","timestamp":1731495066000},"page":"727-742","source":"Crossref","is-referenced-by-count":21,"title":["TRIM21-mediated ubiquitination and phosphorylation of ERK1\/2 promotes cell proliferation and drug resistance in pituitary adenomas"],"prefix":"10.1093","volume":"27","author":[{"given":"Yanting","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical University , Wenzhou ,","place":["China"]},{"name":"Department of Neurosurgery, Center of Pituitary Tumor, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Cell Biology, State Key Laboratory of Oncogenes and Related Genes, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine , Shanghai ,","place":["China"]},{"name":"Department of Neurosurgery, Center of Pituitary Tumor, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanbao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Center of Pituitary Tumor, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical University , Wenzhou ,","place":["China"]},{"name":"Department of Neurosurgery, Center of Pituitary Tumor, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyi","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Center of Pituitary Tumor, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"Dai","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical University , Wenzhou ,","place":["China"]},{"name":"Department of Neurosurgery, Center of Pituitary Tumor, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Center of Pituitary Tumor, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobin","family":"Wang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, Henan University , Kaifeng ,","place":["P.R. 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