Mapk1, also known as mitogen-activated protein kinase 1, is a key component of the MAP kinase signal transduction pathway. It has functions both as a kinase, phosphorylating histones, and as a transcription factor, directly binding to gene promoter regions to regulate gene expression. This dual-functionality makes it crucial in various biological processes and disease-related pathways [2].

In breast cancer, phosphorylation of ULK1 by MAPK1/ERK2-MAPK3/ERK1 kinase triggers ULK1's interaction with BTRC, leading to its K48-linked ubiquitination and proteasome degradation. ULK1 deficiency, induced by MAPK1-mediated degradation, attenuates mitophagy, activates the NLRP3 inflammasome, promotes osteoclast differentiation, and ultimately leads to bone metastasis. The MAP2K/MEK inhibitor trametinib can restore mitophagy by up-regulating ULK1, reducing bone metastasis [1]. In gastric cancer, MAPK1 promotes cell invasion and migration by bidirectionally regulating target genes, up-regulating seven and down-regulating one [2]. In diabetic kidney disease, high glucose increases MAPK1, which lowers the level of PACS-2, disrupting the mitochondria-associated endoplasmic reticulum membrane (MAM) and causing mitochondrial fragmentation. Inhibition of MAPK1 in diabetic mice increases PACS-2 and protects against MAM loss and mitochondrial fragmentation [3].

In summary, Mapk1 is essential in multiple biological processes and disease conditions. Its role in breast cancer bone metastasis, gastric cancer metastasis and invasion, and diabetic kidney disease pathogenesis has been revealed through functional studies. Understanding Mapk1's functions, especially through gene-knockout-based research, provides potential therapeutic targets for these diseases.

References:

1. Deng, Rong, Zhang, Hai-Liang, Huang, Jun-Hao, Tang, Jun, Zhu, Xiao-Feng. 2020. MAPK1/3 kinase-dependent ULK1 degradation attenuates mitophagy and promotes breast cancer bone metastasis. In Autophagy, 17, 3011-3029. doi:10.1080/15548627.2020.1850609. https://pubmed.ncbi.nlm.nih.gov/33213267/

2. Wang, Yue, Guo, Zheng, Tian, Yueli, Li, Xingang, Song, Ying. 2023. MAPK1 promotes the metastasis and invasion of gastric cancer as a bidirectional transcription factor. In BMC cancer, 23, 959. doi:10.1186/s12885-023-11480-3. https://pubmed.ncbi.nlm.nih.gov/37817112/

3. Liu, Shanshan, Han, Shuai, Wang, Cuili, Chen, Jianghua, Jiang, Hong. 2024. MAPK1 Mediates MAM Disruption and Mitochondrial Dysfunction in Diabetic Kidney Disease via the PACS-2-Dependent Mechanism. In International journal of biological sciences, 20, 569-584. doi:10.7150/ijbs.89291. https://pubmed.ncbi.nlm.nih.gov/38169625/