Lee Hye Suk, Cho Sung-Jun, Kang Han Chang, Lee Joo Young, Kwon Young Jik, Cho Yong-Yeon
BK21-4th, College of Pharmacy, The Catholic University of Korea, 43, Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do, 14662, Republic of Korea.
Research Institute for Controlss and Materialss of Regulated Cell Death, The Catholic University of Korea, 43, Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do, 14662, Republic of Korea.
Arch Pharm Res. 2025 May;48(5):365-383. doi: 10.1007/s12272-025-01543-3. Epub 2025 May 5.
The growth factor-mediated mitogen-activated protein kinase (MAPK) signaling pathways in cancer development have become increasingly important in the discovery of therapeutic agents for the treatment of cancer. RSK2 has been historically overlooked in studies regarding its involvement in physiology and signaling pathways related to human diseases, except for Coffin-Lowry syndrome, because it is located downstream of ERKs. For the last 25 years, the authors' laboratory has made groundbreaking discoveries regarding the role of RSK2, especially by elucidating its binding partners, signaling network, and crosstalk. RSK2 is an important emerging target for developing anticancer drugs. Nevertheless, further studies on the detailed mechanism and signaling network are necessary to avoid the unexpected effects of RSK2 inhibitors. This paper describes a new paradigm of RSK2, where it works as a signaling node to modulate diverse cellular processes, including cell proliferation and transformation, cell cycle regulation, chromatin remodeling, and immune response and inflammation regulation.
生长因子介导的丝裂原活化蛋白激酶(MAPK)信号通路在癌症发展过程中,对于发现癌症治疗药物而言愈发重要。历史上,除了科芬-洛里综合征外,在有关RSK2参与人体疾病相关生理学和信号通路的研究中,RSK2一直被忽视,因为它位于细胞外信号调节激酶(ERK)的下游。在过去25年里,作者所在的实验室在RSK2的作用方面取得了开创性发现,尤其是通过阐明其结合伙伴、信号网络和信号转导相互作用。RSK2是开发抗癌药物的一个重要新兴靶点。然而,为避免RSK2抑制剂产生意外效应,有必要对其详细机制和信号网络开展进一步研究。本文描述了RSK2的一种新范式,即它作为一个信号节点来调节多种细胞过程,包括细胞增殖与转化、细胞周期调控、染色质重塑以及免疫反应和炎症调节。