MYLK3,也称为肌球蛋白轻链激酶3,是一种编码心脏肌球蛋白轻链激酶(cMLCK)的基因。cMLCK在心脏收缩功能中发挥重要作用,它通过磷酸化心室肌球蛋白调节轻链(MLC2v)来调节心脏的收缩性。MYLK3的突变与家族性扩张型心肌病(DCM)有关,这是一种以心脏扩大和心力衰竭为特征的疾病。在心脏衰竭患者中,MYLK3的表达水平显著降低,这表明MYLK3的失调可能参与心脏收缩功能障碍的发生。此外,MYLK3的甲基化水平与卵巢癌患者的生存率相关,高甲基化的MYLK3与更好的生存率相关,这可能作为预测手术反应的生物标志物。MYLK3的表达还受到GATA转录因子的调控,这表明MYLK3在红细胞功能和血管发育中可能发挥重要作用。综上所述,MYLK3在心脏功能、疾病发生和红细胞功能中发挥重要作用,对其研究的深入将有助于理解相关疾病的发病机制,并为疾病的治疗和预防提供新的思路和策略[1,2,3,4,5,6,7,8]。
参考文献:
1. Hitsumoto, Tatsuro, Tsukamoto, Osamu, Matsuoka, Ken, Haruta, Jun-Ichi, Takashima, Seiji. 2023. Restoration of Cardiac Myosin Light Chain Kinase Ameliorates Systolic Dysfunction by Reducing Superrelaxed Myosin. In Circulation, 147, 1902-1918. doi:10.1161/CIRCULATIONAHA.122.062885. https://pubmed.ncbi.nlm.nih.gov/37128901/
2. Phelps, David L, Borley, Jane V, Flower, Kirsty J, Brown, Robert, Ghaem-Maghami, Sadaf. 2017. Methylation of MYLK3 gene promoter region: a biomarker to stratify surgical care in ovarian cancer in a multicentre study. In British journal of cancer, 116, 1287-1293. doi:10.1038/bjc.2017.83. https://pubmed.ncbi.nlm.nih.gov/28350786/
3. Ghaderi, Shahrooz, Levkau, Bodo. 2023. An erythrocyte-centric view on the MFSD2B sphingosine-1-phosphate transporter. In Pharmacology & therapeutics, 249, 108483. doi:10.1016/j.pharmthera.2023.108483. https://pubmed.ncbi.nlm.nih.gov/37390971/
4. Min, Kyung-Duk, Asakura, Masanori, Liao, Yulin, Mochizuki, Naoki, Kitakaze, Masafumi. 2010. Identification of genes related to heart failure using global gene expression profiling of human failing myocardium. In Biochemical and biophysical research communications, 393, 55-60. doi:10.1016/j.bbrc.2010.01.076. https://pubmed.ncbi.nlm.nih.gov/20100464/
5. Tobita, Takashige, Nomura, Seitaro, Morita, Hiroyuki, Aburatani, Hiroyuki, Komuro, Issei. 2017. Identification of MYLK3 mutations in familial dilated cardiomyopathy. In Scientific reports, 7, 17495. doi:10.1038/s41598-017-17769-1. https://pubmed.ncbi.nlm.nih.gov/29235529/
6. Tougas, Carson L, Grindrod, Tabor, Cai, Lawrence X, Alkassis, Fariz F, Kasahara, Hideko. 2019. Heterozygous Mylk3 Knockout Mice Partially Recapitulate Human DCM With Heterozygous MYLK3 Mutations. In Frontiers in physiology, 10, 696. doi:10.3389/fphys.2019.00696. https://pubmed.ncbi.nlm.nih.gov/31244672/
7. Williams, Jack L, Paudyal, Anju, Awad, Sherine, Cox, Roger D, Metherell, Lou A. 2020. Mylk3 null C57BL/6N mice develop cardiomyopathy, whereas Nnt null C57BL/6J mice do not. In Life science alliance, 3, . doi:10.26508/lsa.201900593. https://pubmed.ncbi.nlm.nih.gov/32213617/
8. Hajebi Khaniki, Saeedeh, Shokoohi, Farhad, Esmaily, Habibollah, Kerachian, Mohammad Amin. 2023. Analyzing aberrant DNA methylation in colorectal cancer uncovered intangible heterogeneity of gene effects in the survival time of patients. In Scientific reports, 13, 22104. doi:10.1038/s41598-023-47377-1. https://pubmed.ncbi.nlm.nih.gov/38092774/