{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNAP1L1 is a multifunctional histone chaperone that plays a vital role in chromatin dynamics by mediating nucleosome assembly and disassembly. Structural studies have revealed that it consists of a conserved core domain and a flexible acidic C-terminal region, which together facilitate the binding and deposition of histone H2A–H2B dimers. In addition, NAP1L1 associates with key transcription factors and chromatin remodelers—modulating histone acetylation (for example, of p53) and thereby influencing transcriptional activation—to fine‐tune gene expression programs."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAberrant NAP1L1 expression is emerging as a driver of oncogenesis across a variety of tumor types. In hepatocellular carcinoma, for example, oncogenic long noncoding RNAs act through molecular sponging mechanisms to elevate NAP1L1 levels, thereby activating the PI3K/AKT/mTOR pathway and promoting tumor growth and metastasis. Similarly, increased NAP1L1 expression is associated with cell cycle progression and poor clinical outcome in lung adenocarcinoma, ovarian, gastric, and endometrial cancers; its contribution to malignant phenotypes involves activation of signaling cascades such as NF‑κB and Wnt/β‑catenin."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its nuclear functions, NAP1L1 participates in diverse cellular processes that extend to the cytoplasm. It interacts directly with viral proteins—such as hepatitis C virus NS5A, which sequesters NAP1L1 to compromise antiviral signaling, and is also involved in Epstein–Barr virus reactivation by remodeling chromatin at key viral promoters—underscoring its role in host–virus interplay. Furthermore, NAP1L1 accumulates at DNA double strand break sites to assist RAD54-mediated histone eviction during homologous recombination and engages with autophagy receptors (via interactions with NDP52 and TAX1BP1) to modulate selective autophagy. Its involvement in neuronal differentiation (through interactions with other NAP1 family members) and its unexpected partnership with mitochondrial proteins in platelets—impacting pyruvate dehydrogenase complex activity and thrombopoiesis—further emphasize the broad-ranging influence of NAP1L1 on cell homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "15", "end_ref": "21"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Manuela Rehtanz, Hanns-Martin Schmidt, Ursula Warthorst, et al. 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