{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nProhibitin 1 (PHB1) is a multifunctional protein that exerts critical regulatory roles in the nucleus, where it modulates gene transcription, cell‐cycle progression, and tumor suppression. In several cancer models, PHB1 interacts directly with key transcription factors and tumor suppressors—including E2F family members, p53, and nuclear hormone receptors—to repress or activate target gene transcription, thereby controlling proliferation and apoptosis. In addition, PHB1 is subject to post‐transcriptional regulation via microRNAs (for example, miR‑27a in gastric and prostate cancers) and its activity can be modulated through interactions with chromatin remodeling complexes. Collectively, these nuclear functions position PHB1 as a central node in pathways governing cell growth and differentiation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the mitochondria, PHB1 functions as a chaperone and structural scaffold that is essential for maintaining mitochondrial integrity, regulating the organization and copy number of mitochondrial DNA, and modulating reactive oxygen species production. These roles are critical for cellular stress responses, as evidenced by PHB1’s ability to promote senescence, protect against oxidative injury in neurons and retinal pigment epithelial cells, and modulate autophagy and inflammatory signaling in the gastrointestinal tract. Through these mechanisms, PHB1 contributes to the preservation of mitochondrial function under both physiological and stress conditions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "25"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the plasma membrane and in the cytosol, PHB1 is a versatile mediator of key signaling cascades and cellular responses. It is indispensable for Ras‐induced activation of the Raf–MEK–ERK pathway, thereby promoting cell migration and proliferation in oncogenic settings. PHB1 also functions as a cell-surface receptor or cofactor for viral proteins—playing roles in SARS‑CoV, chikungunya virus, HIV‑1, and EV71 infections—and its altered localization has been implicated in chemoresistance (e.g., to paclitaxel) and metastasis. 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