Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan 410078, China.
Cancer Research Institute and School of Basic Medical Science, Central South University, Changsha, Hunan 410078, China.
Int J Cancer. 2019 Sep 15;145(6):1475-1483. doi: 10.1002/ijc.32253. Epub 2019 Mar 26.
Deregulation of cellular metabolism is well established in cancer. The mitochondria are dynamic organelles and act as the center stage for energy metabolism. Central to mitochondrial regulatory network is peroxisome proliferator-activated receptor γ coactivator 1a (PGC-1α), which serves as a master regulator of mitochondrial proliferation and metabolism. The activity and stability of PGC-1α are subject to dynamic and versatile posttranslational modifications including phosphorylation, ubiquitination, methylation and acetylation in response to metabolic stress and other environmental signals. In this review, we describe the structure of PGC-1α. Then, we discuss recent advances in the posttranslational regulatory machinery of PGC-1α, which affects its transcriptional activity, stability and organelle localization. Furthermore, we address the important roles of PGC-1α in tumorigenesis and malignancy. Finally, we also mention the clinical therapeutic potentials of PGC-1α modulators. A better understanding of the elegant function of PGC-1α in cancer progression could provide novel insights into therapeutic interventions through the targeting of PGC-1α signaling.
细胞代谢的失调在癌症中已得到充分证实。线粒体是动态细胞器，是能量代谢的中心舞台。过氧化物酶体增殖物激活受体 γ 共激活因子 1a（PGC-1α）是线粒体调节网络的核心，它作为线粒体增殖和代谢的主调控因子。PGC-1α 的活性和稳定性受到多种翻译后修饰的影响，包括磷酸化、泛素化、甲基化和乙酰化，以响应代谢应激和其他环境信号。在这篇综述中，我们描述了 PGC-1α 的结构。然后，我们讨论了 PGC-1α 的翻译后调节机制的最新进展，这些机制影响其转录活性、稳定性和细胞器定位。此外，我们还探讨了 PGC-1α 在肿瘤发生和恶性肿瘤中的重要作用。最后，我们还提到了 PGC-1α 调节剂的临床治疗潜力。更好地理解 PGC-1α 在癌症进展中的精细功能，可以通过靶向 PGC-1α 信号提供治疗干预的新见解。
