{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Kelch repeat and BTB domain‐containing protein 11 (KBTBD11) is emerging as a multifunctional regulator in diverse physiological and pathological settings. Initially identified during large‐scale sequencing projects in human brain cDNA libraries"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ", KBTBD11 has been implicated in the regulation of cell signaling, proliferation, and differentiation. In colorectal cancer, a polymorphism (rs11777210) within KBTBD11 is significantly associated with disease susceptibility, and functional studies have demonstrated that MYC can bind to and negatively regulate KBTBD11 expression when the risk allele is present; reduced levels of KBTBD11 promote cell proliferation and impair apoptosis, supporting its role as a putative tumor suppressor."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Moreover, in adipocyte biology, KBTBD11 expression is nutritionally regulated—its levels increase during refeeding and obesity—and experimental modulation in preadipocytes confirms that KBTBD11 is required for effective adipocyte differentiation and triglyceride accumulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In addition to these roles, studies of gene methylation further reveal that differential allele‐specific methylation of KBTBD11 is associated with immune phenotypes and distinguishes subtypes of pediatric acute lymphoblastic leukemia, highlighting its potential as a biomarker in oncology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Finally, in the context of bone biology, KBTBD11 acts as a negative regulator of osteoclast differentiation by interacting with the E3 ubiquitin ligase Cullin3 to promote the ubiquitination and proteasomal degradation of NFATc1, a key transcription factor driving osteoclastogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Collectively, these findings indicate that KBTBD11 occupies a central role in modulating tumorigenesis, metabolic regulation, immune function, and bone remodeling.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "T Nagase, K Ishikawa, M Suyama, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Prediction of the coding sequences of unidentified human genes. XI. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "DNA Res (1998)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/dnares/5.5.277"}], "href": "https://doi.org/10.1093/dnares/5.5.277"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "9872452"}], "href": "https://pubmed.ncbi.nlm.nih.gov/9872452"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "J Gong, J Tian, J Lou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A polymorphic MYC response element in KBTBD11 influences colorectal cancer risk, especially in interaction with an MYC-regulated SNP rs6983267."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Oncol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/annonc/mdx789"}], "href": "https://doi.org/10.1093/annonc/mdx789"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29267898"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29267898"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Kazuhisa Watanabe, Ken Yoshida, Sadahiko Iwamoto "}, {"type": "b", "children": [{"type": "t", "text": "Kbtbd11 gene expression in adipose tissue increases in response to feeding and affects adipocyte differentiation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Diabetes Investig (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jdi.12995"}], "href": "https://doi.org/10.1111/jdi.12995"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30582777"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30582777"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Priyadarshini Kachroo, Silke Szymczak, Femke-Anouska Heinsen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NGS-based methylation profiling differentiates TCF3-HLF and TCF3-PBX1 positive B-cell acute lymphoblastic leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Epigenomics (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2217/epi-2017-0080"}], "href": "https://doi.org/10.2217/epi-2017-0080"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29334255"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29334255"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Shun Narahara, Eiko Sakai, Tomoko Kadowaki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "KBTBD11, a novel BTB-Kelch protein, is a negative regulator of osteoclastogenesis through controlling Cullin3-mediated ubiquitination of NFATc1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-019-40240-2"}], "href": "https://doi.org/10.1038/s41598-019-40240-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30837587"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30837587"}]}]}]}