{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPPP1CA, which encodes the catalytic subunit PP1α of the ubiquitous serine/threonine protein phosphatase 1, is central to the fine‐tuning of phosphorylation events that dictate key cellular responses. For example, PP1α acts in innate immunity by dephosphorylating the caspase recruitment domains of cytosolic sensors such as RIG‑I and MDA5—thereby promoting type‑I interferon production—and additionally cooperates with PP2B to dephosphorylate phospho‑Thr186 in the Cdk9 T‑loop, a critical step in releasing the active transcription factor P‑TEFb."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBy forming distinct holoenzymes through interactions with a diverse array of regulatory proteins, PP1α achieves remarkable substrate specificity. In several contexts, PP1α dephosphorylates key transcriptional regulators—for instance, it dephosphorylates TAZ at Ser‑89 and Ser‑311 to promote its nuclear translocation and stability, modulates Wnt/β‑catenin signaling by dephosphorylating axin, and directly targets AKT (particularly at Thr‑450) to modulate survival signaling. Likewise, its actions on the androgen receptor and MEF2 integrate signals that control receptor stability, transcriptional activation and cell differentiation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond the regulation of signaling and transcription, PP1α plays vital roles in modulating cytoskeletal dynamics, cell cycle progression, and apoptosis. Its dephosphorylation of substrates such as ERM proteins and tensin1 influences cell adhesion, polarity and migration, while aberrant PPP1CA gene amplification has been implicated in tumorigenesis—for example, in oral squamous cell carcinoma—and hyperactivation of MAPK signaling in metastatic cancers. Moreover, under stress conditions PP1α is dynamically controlled by interacting partners (e.g. Rif1 and LAP1B) and is subject to post‑translational modifications (as seen in responses to hydrogen sulfide), thereby integrating cues that affect DNA replication, transcription elongation and programmed cell death."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Effi Wies, May K Wang, Natalya P Maharaj, et al. 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