School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China.
Int J Mol Sci. 2023 Mar 27;24(7):6264. doi: 10.3390/ijms24076264.
We have previously reported as a muscle-specific gene that represses myoblast proliferation and promotes myogenic differentiation. The regulatory mechanism of gene expression has been well clarified recently. However, the underlying mechanism of Tceal7 function in skeletal muscle development remains to be elucidated. In the present study, we have generated an MCK 6.5 kb-HA-Tceal7 transgenic model. The transgenic mice are born normally, while they have displayed defects in the growth of body weight and skeletal muscle myofiber during postnatal development. Although four RxL motifs have been identified in the Tceal7 protein sequence, we have not detected any direct protein-protein interaction between Tceal7 and Cyclin A2, Cyclin B1, Cylin D1, or Cyclin E1. Further analysis has revealed the interaction between Tceal7 and Cdk1 instead of Cdk2, Cdk4, or Cdk6. Transgenic overexpression of Tceal7 reduces phosphorylation of 4E-BP1 Ser65, p70S6K1 Thr389, and Cdk substrates in skeletal muscle. In summary, these studies have revealed a novel mechanism of Tceal7 in skeletal muscle development.
我们之前报道过，它是一种肌肉特异性基因，可抑制成肌细胞增殖并促进成肌分化。最近， 基因表达的调控机制已经得到了很好的阐明。然而，Tceal7 在骨骼肌发育中的功能的潜在机制仍有待阐明。在本研究中，我们构建了一个 MCK 6.5 kb-HA-Tceal7 转基因模型。转基因小鼠正常出生，但在出生后发育过程中体重和骨骼肌肌纤维的生长出现缺陷。尽管在 Tceal7 蛋白序列中鉴定出了四个 RxL 基序，但我们尚未检测到 Tceal7 与细胞周期蛋白 A2、B1、D1 或 E1 之间的任何直接蛋白-蛋白相互作用。进一步的分析揭示了 Tceal7 与 Cdk1 而不是 Cdk2、Cdk4 或 Cdk6 之间的相互作用。Tceal7 的转基因过表达降低了骨骼肌中 4E-BP1 Ser65、p70S6K1 Thr389 和 Cdk 底物的磷酸化。总之，这些研究揭示了 Tceal7 在骨骼肌发育中的一种新的作用机制。
