PKNOX2,全称为PBX/Knotted 1 homeobox-2,是一种编码TALE(Three Amino acid Loop Extension)家族的转录因子,该家族成员在细胞增殖和分化中发挥关键的调控作用。TALE蛋白是高度保守的转录调控因子,在细胞功能的调节中发挥着重要作用,尤其是在细胞增殖和分化方面[2]。
PKNOX2蛋白由460个氨基酸组成,包含HR1、HR2和homeodomain等结构域,这些结构域与PKNOX1具有高度相似性。PKNOX2与PBX蛋白相互作用,可能参与组织特异性的转录调控[2]。PKNOX2在染色体11q24区域上定位,与PKNOX1的基因组结构相似,但PKNOX2的表达模式比PKNOX1更为局限[2]。
PKNOX2在多种生物学过程中发挥着重要作用。例如,在心脏中,PKNOX2被鉴定为一种新的调节因子,与生理性成纤维细胞活化相关。研究显示,PKNOX2在心脏成纤维细胞中发挥着抑制病理性纤维化重塑的作用[1]。此外,PKNOX2在肺癌细胞中通过抑制PI3K/AKT/mTOR信号通路,抑制肺癌细胞增殖[3]。在听觉系统中,PKNOX2对哺乳动物耳蜗的敏感性,特别是在高频听力方面,起着关键作用[4]。
此外,PKNOX2在精神疾病中也发挥着作用。研究表明,PKNOX2与精神分裂症的正式思维障碍有关[10]。另外,PKNOX2与欧洲起源女性的物质依赖性有关[5,6],尽管这一发现后来被撤销[8]。在胃腺癌中,PKNOX2通过转录激活IGFBP5和p53,抑制胃癌细胞的增殖、迁移和侵袭[7]。
在发育过程中,PKNOX2在肢体发育中也发挥着重要作用。研究表明,PKNOX2在胚胎期小鼠肢芽间充质中表达,并调节Hox基因的表达,影响肢体发育[9]。
综上所述,PKNOX2是一种重要的转录因子,在多种生物学过程中发挥着关键作用,包括心脏纤维化、癌症、精神疾病和肢体发育等。PKNOX2的研究有助于深入理解其在生物学过程中的功能,为相关疾病的治疗和预防提供新的思路和策略。
参考文献:
1. Chen, Liang, Li, Haotong, Liu, Xiaorui, Li, Xiangjie, Hu, Shengshou. 2024. PBX/Knotted 1 homeobox-2 (PKNOX2) is a novel regulator of myocardial fibrosis. In Signal transduction and targeted therapy, 9, 94. doi:10.1038/s41392-024-01804-5. https://pubmed.ncbi.nlm.nih.gov/38644381/
2. Imoto, I, Sonoda, I, Yuki, Y, Inazawa, J. . Identification and characterization of human PKNOX2, a novel homeobox-containing gene. In Biochemical and biophysical research communications, 287, 270-6. doi:. https://pubmed.ncbi.nlm.nih.gov/11549286/
3. Song, Minglei, Zhang, Nan, Cao, Fumin, Liu, Junfeng. 2023. PKNOX2 suppresses lung cancer cell proliferation by inhibiting the PI3K/AKT/mTOR axis. In Experimental and therapeutic medicine, 25, 217. doi:10.3892/etm.2023.11917. https://pubmed.ncbi.nlm.nih.gov/37123214/
4. Trigila, Anabella P, Castagna, Valeria C, Berasain, Lara, Gomez-Casati, Maria Eugenia, Franchini, Lucía F. . Accelerated Evolution Analysis Uncovers PKNOX2 as a Key Transcription Factor in the Mammalian Cochlea. In Molecular biology and evolution, 40, . doi:10.1093/molbev/msad128. https://pubmed.ncbi.nlm.nih.gov/37247388/
5. Chen, Xiang, Cho, Kelly, Singer, Burton H, Zhang, Heping. 2009. PKNOX2 gene is significantly associated with substance dependence in European-origin women. In Proceedings of the National Academy of Sciences of the United States of America, , None. doi:. https://pubmed.ncbi.nlm.nih.gov/19721000/
6. Chen, Xiang, Cho, Kelly, Singer, Burton H, Zhang, Heping. 2011. The nuclear transcription factor PKNOX2 is a candidate gene for substance dependence in European-origin women. In PloS one, 6, e16002. doi:10.1371/journal.pone.0016002. https://pubmed.ncbi.nlm.nih.gov/21298047/
7. Zhang, Li, Li, Weilin, Cao, Lei, Wong, Chi Chun, Yu, Jun. 2019. PKNOX2 suppresses gastric cancer through the transcriptional activation of IGFBP5 and p53. In Oncogene, 38, 4590-4604. doi:10.1038/s41388-019-0743-4. https://pubmed.ncbi.nlm.nih.gov/30745575/
8. Chen, Xiang, Cho, Kelly, Singer, Burton H, Zhang, Heping. 2009. Retraction. PKNOX2 gene is significantly associated with substance dependence in European-origin women. In Proceedings of the National Academy of Sciences of the United States of America, 106, 17241. doi:10.1073/pnas.0910252106. https://pubmed.ncbi.nlm.nih.gov/19805159/
9. Zhou, Wenrong, Zhu, Huang, Zhao, Jianzhi, Yao, Zhengju, Guo, Xizhi. 2013. Misexpression of Pknox2 in mouse limb bud mesenchyme perturbs zeugopod development and deltoid crest formation. In PloS one, 8, e64237. doi:10.1371/journal.pone.0064237. https://pubmed.ncbi.nlm.nih.gov/23717575/
10. Wang, Ke-Sheng, Zhang, Qunyuan, Liu, Xuefeng, Wu, Longyang, Zeng, Min. 2012. PKNOX2 is associated with formal thought disorder in schizophrenia: a meta-analysis of two genome-wide association studies. In Journal of molecular neuroscience : MN, 48, 265-72. doi:10.1007/s12031-012-9787-4. https://pubmed.ncbi.nlm.nih.gov/22648509/