{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPolo‐like kinase 3 (Plk3) is emerging as a multifunctional serine/threonine kinase that not only belongs to the polo‐like kinase family—which includes members such as Fnk with tightly regulated expression through nucleocytoplasmic trafficking and proteasome‐mediated degradation (PMID"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "—but also plays a key role in cell cycle regulation. Studies have shown that Plk3 is required during early G1 for cyclin E induction and the G1/S transition, with its levels peaking in G1 phase to drive proper cell cycle reentry (PMID."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its cell cycle–governing functions, Plk3 is a central mediator of cellular stress responses. Its activity is crucial for modulating the hypoxia response, as it phosphorylates hypoxia-inducible factor‑1α (HIF‑1α) to regulate its nuclear accumulation and stability, thereby impacting angiogenesis and tumor progression when dysregulated (PMID"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "; PMID."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Furthermore, Plk3 governs mRNA turnover by interfacing with RNA‐binding proteins such as tristetraprolin, which engages AU-rich elements in its own transcript to ensure proper regulation of its expression (PMID."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In parallel, Plk3 phosphorylates key substrates like PTEN, thereby influencing the PI3K/PDK1/Akt pathway and enforcing growth-suppressive signaling (PMID."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its canonical roles in cell cycle control and stress signaling, Plk3 functions in multiple tissue-specific and oncogenic contexts. In megakaryocytes, for instance, Plk3 interacts with calcium- and integrin-binding proteins (e.g., CIB1) to modulate endomitosis and platelet marker expression (PMID"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ", while its expression during retinogenesis suggests involvement as cells exit the cell cycle (PMID."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " In lung and pancreatic cancers, Plk3 has been implicated in mutant p53-dependent transactivation and, when proteolytically processed into an active form, it promotes apoptotic pathways to counteract tumorigenesis and metastasis (PMID"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "; PMID."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Moreover, in glioblastoma cells, Plk3 is sequestered by tubulin alpha 1a, resulting in a disruption of proper mitotic progression (PMID"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ", and its role in renal ischemia-reperfusion injury further extends its importance in stress-associated tissue damage (PMID."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Gregory F Alberts, Jeffrey A Winkles "}, {"type": "b", "children": [{"type": "t", "text": "Murine FGF-inducible kinase is rapidly degraded via the nuclear ubiquitin-proteosome system when overexpressed in NIH 3T3 cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Cycle (2004)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15107614"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15107614"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Wendy C Zimmerman, Raymond L Erikson "}, {"type": "b", "children": [{"type": "t", "text": "Polo-like kinase 3 is required for entry into S phase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0610856104"}], "href": "https://doi.org/10.1073/pnas.0610856104"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17264206"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17264206"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yali Yang, Jingxiang Bai, Rulong Shen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Polo-like kinase 3 functions as a tumor suppressor and is a negative regulator of hypoxia-inducible factor-1 alpha under hypoxic conditions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-07-6182"}], "href": "https://doi.org/10.1158/0008-5472.CAN-07-6182"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18519666"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18519666"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Dazhong Xu, Yixin Yao, Luo Lu, et al. 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