{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nBMAL2, a member of the basic helix–loop–helix PER–ARNT–SIM family, functions as a core transcriptional regulator of the circadian clock by heterodimerizing with CLOCK. Alternative splicing of BMAL2 generates multiple isoforms with a wide range of transcriptional activities, thereby providing tissues with a flexible “rheostat” to fine‐tune the amplitudes of both central and peripheral circadian oscillators. Moreover, BMAL2 displays distinct transcriptional activation properties compared with its paralog BMAL1, including differential modulation by negative regulators such as PER2 and CRY2 that depend on the specific E-box elements in target promoters."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAlterations in BMAL2 expression and genetic variation have been implicated in neurological and metabolic disorders. For example, decreased BMAL2 expression in total leukocytes has been observed in patients with Parkinson’s disease, suggesting a disturbance of the molecular clock in this neurodegenerative condition. Furthermore, polymorphisms in BMAL2 are associated with Alzheimer’s disease susceptibility—particularly among APOE ε4 non-carriers—and BMAL2 has been evaluated as a candidate gene affecting glucose homeostasis and type 2 diabetes risk."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its canonical role in circadian regulation, BMAL2 (also known as ARNTL2) contributes to immune and oncogenic processes. In the context of inflammatory responses, BMAL2 is induced by extracellular cold-inducible RNA-binding protein and promotes macrophage endotoxin tolerance via TREM-1 signaling. In addition, increased BMAL2/ARNTL2 expression has been linked to the progression of several cancers—including bladder cancer, acute myeloid leukemia, and nasopharyngeal carcinoma—by enhancing cell proliferation, migration, invasion, and metastasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "John A Schoenhard, Mesut Eren, Carl H Johnson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Alternative splicing yields novel BMAL2 variants: tissue distribution and functional characterization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Cell Physiol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpcell.00541.2001"}], "href": "https://doi.org/10.1152/ajpcell.00541.2001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12055078"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12055078"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Momoko Sasaki, Hikari Yoshitane, Ngoc-Hien Du, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Preferential inhibition of BMAL2-CLOCK activity by PER2 reemphasizes its negative role and a positive role of BMAL2 in the circadian transcription."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.040758"}], "href": "https://doi.org/10.1074/jbc.M109.040758"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19605937"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19605937"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Hui Ding, Shu Liu, Yanpeng Yuan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Decreased expression of Bmal2 in patients with Parkinson's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurosci Lett (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neulet.2011.05.058"}], "href": "https://doi.org/10.1016/j.neulet.2011.05.058"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21658431"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21658431"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Liu Qing-Xiu, Huang Chang-Quan, Chen Qian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The polymorphism of ARNTL2 (BMAL2) gene rs2306074 C>T is associated with susceptibility of Alzheimer disease in Chinese population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurol Sci (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10072-014-1824-3"}], "href": "https://doi.org/10.1007/s10072-014-1824-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24847962"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24847962"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Miwa Yamaguchi, Hirokazu Uemura, Kokichi Arisawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association between brain-muscle-ARNT-like protein-2 (BMAL2) gene polymorphism and type 2 diabetes mellitus in obese Japanese individuals: A cross-sectional analysis of the Japan Multi-institutional Collaborative Cohort Study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes Res Clin Pract (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.diabres.2015.10.009"}], "href": "https://doi.org/10.1016/j.diabres.2015.10.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26497775"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26497775"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Mian Zhou, Monowar Aziz, Jingsong Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "BMAL2 promotes eCIRP-induced macrophage endotoxin tolerance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Immunol (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fimmu.2024.1426682"}], "href": "https://doi.org/10.3389/fimmu.2024.1426682"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38938563"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38938563"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Jiahao Wang, Junwei Ren, Xiang Tu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ARNTL2 facilitates bladder cancer progression through potentiating ENO1-mediated glycolysis in a SLC31A1-independent and -dependent manner."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Life Sci (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.lfs.2024.122974"}], "href": "https://doi.org/10.1016/j.lfs.2024.122974"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "39147318"}], "href": "https://pubmed.ncbi.nlm.nih.gov/39147318"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Wei-Jing Jia, Jiao Mu, Wen-Jing Cui "}, {"type": "b", "children": [{"type": "t", "text": "[Effects of BMAL2 on Aerobic Glycolysis and Cell Proliferation in Acute Myeloid Leukemia Cells]."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Zhongguo Shi Yan Xue Ye Xue Za Zhi (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.19746/j.cnki.issn.1009-2137.2024.02.012"}], "href": "https://doi.org/10.19746/j.cnki.issn.1009-2137.2024.02.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38660843"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38660843"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Wenqing Zou, Yiming Lei, Cong Ding, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The circadian gene ARNTL2 promotes nasopharyngeal carcinoma invasiveness and metastasis through suppressing AMOTL2-LATS-YAP pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-024-06860-x"}], "href": "https://doi.org/10.1038/s41419-024-06860-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38956029"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38956029"}]}]}]}