{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNIFK functions as a critical binding partner of the proliferation marker Ki67 through its interaction with Ki67’s forkhead‐associated (FHA) domain. Structural studies using peptide fragments of hNIFK have revealed that this interaction involves a 44–residue region centered on a key phosphorylated threonine (pThr234-Pro235) and an extended binding surface that is further stabilized by aromatic‐mediated anchoring, ensuring the correct alignment of the intermolecular β‐sheet. These insights illuminate how NIFK modulates Ki67’s roles in cell proliferation by forming a structurally specific complex."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in protein–protein interactions, NIFK is essential for proper ribosome biogenesis and cell cycle progression. Transactivated by c-Myc, NIFK employs its RNA recognition motif (RRM) to bind preferentially to the 5′-region of the internal transcribed spacer 2 (ITS2) in pre-rRNA, thereby facilitating the crucial cleavage events required for the maturation of 28S and 5.8S rRNA. Loss of NIFK function disrupts this process, leading to nucleolar stress, a p53-dependent G1 arrest, and consequent inhibition of cell proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nEmerging evidence also implicates NIFK as a key player in tumor progression and metastasis. Elevated expression of NIFK is clinically associated with poor prognosis in lung cancer, where it enhances Ki67-dependent proliferation and promotes migration, invasion, and metastasis through the repression of casein kinase 1α (CK1α) and subsequent activation of pro-metastatic TCF4/β-catenin signaling, partly via RUNX1-mediated mechanisms. Similarly, its expression in colorectal cancer is being investigated for correlations with tumor immune infiltration and adverse clinical outcomes, suggesting that aberrant NIFK activity may serve as both a driver of oncogenesis and a prognostic biomarker."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hongyuan Li, In Ja L Byeon, Yong Ju, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structure of human Ki67 FHA domain and its binding to a phosphoprotein fragment from hNIFK reveal unique recognition sites and new views to the structural basis of FHA domain functions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Biol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jmb.2003.10.032"}], "href": "https://doi.org/10.1016/j.jmb.2003.10.032"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14659764"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14659764"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Maria T Panteva, Reza Salari, Monica Bhattacharjee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Direct observations of shifts in the β-sheet register of a protein-peptide complex using explicit solvent simulations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biophys J (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bpj.2011.03.035"}], "href": "https://doi.org/10.1016/j.bpj.2011.03.035"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21539773"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21539773"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Wen-An Pan, Hsin-Yue Tsai, Shun-Chang Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The RNA recognition motif of NIFK is required for rRNA maturation during cell cycle progression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "RNA Biol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15476286.2015.1017221"}], "href": "https://doi.org/10.1080/15476286.2015.1017221"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25826659"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25826659"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Tsung-Chieh Lin, Chia-Yi Su, Pei-Yu Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The nucleolar protein NIFK promotes cancer progression via CK1α/β-catenin in metastasis and Ki-67-dependent cell proliferation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.11288"}], "href": "https://doi.org/10.7554/eLife.11288"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26984280"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26984280"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Lin Tan, Yuqi He, Linhui Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NIFK as a potential prognostic biomarker in colorectal cancer correlating with immune infiltrates."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Medicine (Baltimore) (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/MD.0000000000035452"}], "href": "https://doi.org/10.1097/MD.0000000000035452"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37800782"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37800782"}]}]}]}