Sox6 suppression induces RA-dependent apoptosis mediated by BMP-4 expression during neuronal differentiation in P19 cells

作者：Hamada Kanazawa Michiko^*; Ogawa Daisuke; Takano Masaoki; Miyake Masaharu

来源：Molecular and Cellular Biochemistry, 2016, 412(1-2): 49-57.

DOI：10.1007/s11010-015-2607-8

• Sox6
• P19
• BMP-4
• Retinoic acid
• Apoptosis
• BMPRIB

Sox6 is a transcription factor that induces neuronal differentiation in P19 cells; its suppression not only inhibits neuronal differentiation but also induces retinoic acid (RA)-dependent apoptosis of P19 cells. In the present study, we found that Sox6 suppression-induced apoptosis was mediated by activation of caspase 9 and 3. Moreover, we noted a weak leakage of cytochrome c into the cytoplasm from the mitochondria, indicating that apoptosis occurs through a mitochondrial pathway in Sox6-suppressed P19 (P19[anti-Sox6]) cells. Sox6 suppression in the presence of RA also induced the expression and secretion of bone morphogenetic protein 4 (BMP-4). Addition of an anti-BMP-4 antibody for neutralization increased cell viability and led to RA-dependent death of P19[anti-Sox6] cells. Our results indicate that Sox6 suppression induces RA-dependent cell death of P19 cells, mediated by BMP-4 expression and secretion. Normally, high Sox6 expression leads to RA-mediated neuronal differentiation in P19 cells; however, Sox6 deficiency induces production and secretion of BMP-4, which mediates selective cell death. Our findings suggest that Sox6 contributes to cell survival by suppressing BMP-4 transcription during neuronal differentiation.

• 出版日期2016-1