Rediscovery of PHI-1/PPP1R14B: Emerging Roles of Cellular PP1 Signaling Mediated by the <i>PPP1R14B</i> Gene Product in Multiple Cancers and Beyond
PHI-1, encoded by <i>PPP1R14B</i>, regulates cellular protein phosphatase-1 (PP1) signaling and has emerged as both a biomarker and therapeutic target. Initially identified as a phospholipase-neighboring gene (PNG), PHI-1 is now known for its phosphorylation-dependent inhibition of PP1 h...
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| Format: | Article |
| Language: | English |
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MDPI AG
2025-02-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/15/3/344 |
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| Summary: | PHI-1, encoded by <i>PPP1R14B</i>, regulates cellular protein phosphatase-1 (PP1) signaling and has emerged as both a biomarker and therapeutic target. Initially identified as a phospholipase-neighboring gene (PNG), PHI-1 is now known for its phosphorylation-dependent inhibition of PP1 holoenzymes, with bi-directional roles depending on its expression levels. Under physiological conditions, PHI-1 selectively regulates PP1 activity to maintain cellular homeostasis, whereas its pathological upregulation promotes oncogenic pathways, stabilizes tumor-promoting proteins, and modulates immune responses. This article explores PHI-1’s emerging role as a pan-cancer biomarker in parallel with emphasizing its physiological functions in signaling networks, smooth muscle contraction, cytoskeletal dynamics, and selective proteostasis. The mechanistic insights highlight PHI-1’s potential in precision oncology, offering opportunities for developing diagnostics and therapies that target its conditional functions. |
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| ISSN: | 2218-273X |