Okamoto S, Krainc D, Sherman K, Lipton S A
Center for Neuroscience and Aging, The Burnham Institute, La Jolla, CA 92037, USA.
Proc Natl Acad Sci U S A. 2000 Jun 20;97(13):7561-6. doi: 10.1073/pnas.130502697.
Myocyte enhancer factor 2 (MEF2) is in the MADS (MCM1agamous-deficiens-serum response factor) family of transcription factors. Although MEF2 is known as a myogenic factor, the expression pattern of the MEF2 family of genes (MEF2A-D) in developing brain also suggests a role in neurogenesis. Here we show that transfection with MEF2C, the predominant form in mammalian cerebral cortex, induces a mixed neuronal/myogenic phenotype in undifferentiated P19 precursor cells. During retinoic acid-induced neurogenesis of these cells, a dominant negative form of MEF2 enhances apoptosis but does not affect cell division. The mitogen-activated protein kinase p38alpha activates MEF2C. Dominant negative p38alpha also enhances apoptotic death of differentiating neurons, but these cells can be rescued from apoptosis by coexpression of constitutively active MEF2C. These findings suggest that the p38alpha/MEF2 pathway prevents cell death during neuronal differentiation.
肌细胞增强因子2（MEF2）属于转录因子的MADS（MCM1、无配子生殖、血清反应因子）家族。尽管MEF2作为一种生肌因子而为人所知，但MEF2基因家族（MEF2A - D）在发育中的大脑中的表达模式也提示其在神经发生过程中发挥作用。在此我们表明，用哺乳动物大脑皮层中主要形式的MEF2C进行转染，可在未分化的P19前体细胞中诱导出混合的神经元/肌源性表型。在这些细胞的视黄酸诱导神经发生过程中，MEF2的显性负性形式会增强细胞凋亡，但不影响细胞分裂。丝裂原活化蛋白激酶p38α可激活MEF2C。显性负性p38α也会增强分化中神经元的凋亡性死亡，但通过共表达组成型活性MEF2C可使这些细胞免于凋亡。这些发现表明，p38α/MEF2信号通路可防止神经元分化过程中的细胞死亡。
