Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
J Biol Chem. 2010 Jan 29;285(5):3462-9. doi: 10.1074/jbc.M109.053587. Epub 2009 Nov 16.
Proinsulin C-peptide is internalized into cells, but a function of its intracellular localization has not been established. We now demonstrate that, upon cellular entry, C-peptide is localized to the nucleoli, where it promotes transcription of genes encoding for ribosomal RNA. We find that C-peptide binds to histones and enhances acetylation of lysine residue 16 of histone H4 at the promoter region of genes for ribosomal RNA. In agreement with synchrony of ribosomal RNA synthesis and cell proliferation, we show that C-peptide stimulates proliferation in chondrocytes and HEK-293 cells. This regulation of ribosomal RNA provides a mechanism by which C-peptide can exert transcriptional effects and implies that the peptide has growth factor activity.
胰岛素原 C 肽被内吞到细胞内，但它的细胞内定位的功能尚未确定。我们现在证明，在进入细胞后，C 肽定位于核仁，在那里它促进核糖体 RNA 编码基因的转录。我们发现 C 肽与组蛋白结合，并增强核糖体 RNA 基因启动子区域组蛋白 H4 赖氨酸残基 16 的乙酰化。与核糖体 RNA 合成和细胞增殖的同步性一致，我们表明 C 肽刺激软骨细胞和 HEK-293 细胞的增殖。这种对核糖体 RNA 的调节提供了 C 肽可以发挥转录作用的机制，并暗示该肽具有生长因子活性。
