{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n FEM1B is an evolutionarily conserved adapter protein that functions as a substrate‐recognition subunit of CUL2–RING E3 ubiquitin ligase complexes, where it selectively binds proteins bearing Arg/C‐degron motifs to promote their ubiquitination and proteasomal degradation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition to its central role in proteostasis, FEM1B contributes to cell cycle regulation—for example, by modulating the levels of components such as the stem–loop binding protein involved in histone mRNA metabolism during S‐phase."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Its pro‐apoptotic functions have been highlighted in contexts such as colon cancer, where FEM1B expression and stability influence programmed cell death, with its degradation being mediated in part by interacting proteins like RACK1."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": " FEM1B also regulates transcriptional programs by binding factors such as Gli1, thereby repressing oncogenic signaling cascades."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Moreover, studies in animal models indicate that FEM1B is important for metabolic homeostasis; knockout experiments reveal defects in glucose‐stimulated insulin secretion and abnormal glucose tolerance"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ", and genetic association studies further link FEM1B variants with polycystic ovary syndrome and type 2 diabetes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "11"}]}, {"type": "t", "text": " In the reproductive system, FEM1B is expressed in the testes and is implicated in spermatogenesis, in part through interactions with partners such as PHTF1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Emerging evidence further shows that modulation of FEM1B levels—for instance, via interaction with long noncoding RNAs in glioma"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "or by covalent targeting with small molecules to disrupt its binding to natural substrates involved in the reductive stress response"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": "—can have profound effects on cell signaling and viability. Finally, FEM1B has been identified as a candidate gene associated not only with cellular processes that impact cancer cell chemosensitivity"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": "but also with broader physiological traits including aspects of feed efficiency in agricultural species and even neurodevelopment, as indicated by emerging genetic studies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "17", "end_ref": "19"}]}, {"type": "t", "text": " Collectively, these findings underscore the multifaceted role of FEM1B as a regulator of protein turnover, apoptosis, metabolic control, and development, thereby highlighting its potential as both a biomarker and a therapeutic target in diverse human diseases.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Xinyan Chen, Shanhui Liao, Yaara Makaros, et al. 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