{"database":"iProX","file_versions":[],"scores":null,"additional":{"omics_type":["Proteomics"],"submitter":["Lingyun Dai"],"species":["Homo Sapiens"],"full_dataset_link":["http://www.iprox.org/page/project.html?id=IPX0016340000"],"submitter_email":["lingyun.dai@outlook.com"],"submitter_affiliation":["the First Affiliated Hospital of Southern University of Science and Technology"],"sample_protocol":[""],"repository":["iProX"],"data_protocol":[""],"pubmed_abstract":["Selenium maintains cellular redox homeostasis primarily through its incorporation into selenoproteins. However, whether and how selenium metabolism modulates oxidative phosphorylation (OXPHOS), a major endogenous source of oxidative stress, has remained unclear. Here, we performed an OXPHOS-focused screen targeting selenium-metabolizing enzymes and identified SEPHS2 as a central hub linking selenium metabolism to OXPHOS. SEPHS2 knockout suppresses OXPHOS while retaining glucose as the primary carbon source of cellular respiration and redirecting glucose metabolism toward gluconeogenesis and the downstream pentose phosphate pathway (PPP). Mechanistically, SEPHS2 loss elevates intracellular NAD<sup>+</sup> levels, thereby activating the deacetylase SIRT2 as a cofactor and promoting deacetylation-dependent stabilization of the gluconeogenic enzyme PCK1. Under selenium-limited conditions, SEPHS2 is reduced. SEPHS2 loss promotes tumor spread to the lung and sensitizes tumors to the PPP inhibitor 6-aminonicotinamide. These findings define a selenoprotein biosynthesis-independent role of SEPHS2 in regulating OXPHOS and unveil the PPP as a therapeutic vulnerability in tumors adapting to a selenium-limited microenvironment."],"pubmed_title":["SEPHS2 loss reprograms cancer metabolism from oxidative phosphorylation to gluconeogenesis via PCK1 stabilization."],"pubmed_authors":["Zhang Yihuizhi Y, Zhang Qinghua Q, Wei Bi B, Wang Wenzhou W, Chen Xinyu X, Ding Weijian W, Li Chenguang C, Ye Yirui Y, Xu Jiali J, Zhang Weibo W, Li Linyue L, Mai Fengyi F, He Wenyou W, Du Xiancai X, Zhao Keyu K, Zhao Zining Z, Huang Jingnan J, Niu Yuchun Y, Zhang Yue Y, Dai Lingyun L, Zhang Baotong B, Xia Siyuan S"],"additional_accession":[]},"is_claimable":false,"name":"SEPHS2 loss reprograms cancer metabolism from oxidative phosphorylation to gluconeogenesis via PCK1 stabilization","description":"SEPHS2, a key enzyme in synthesizing selenoproteins, which converts hydrogen selenide into selenophosphate. Here we provide the proteome of SEPHS2 knockout human A375 celllines.","dates":{"publication":"Wed Mar 25 00:00:00 GMT 2026"},"accession":"PXD076137","cross_references":{"TAXONOMY":["9606"],"pubmed":["42035418"]}}