期刊
BIOMOLECULES
卷 11, 期 10, 页码 -出版社
MDPI
DOI: 10.3390/biom11101444
关键词
cell cycle; cell signaling; apoptosis; mitosis; chemotherapy; kinase; protein networks; DNA damage; cell stress
资金
- National Institutes of Health/National Institute of General Medical Sciences [R01GM083024, R01GM102413, R35GM141833]
- National Institutes of Health/National Cancer Institute [T32CA009156]
Protein signaling networks are formed by diverse and interconnected cell signaling pathways, with the mitogen activated protein kinases (MAPKs) being important components in transmitting signals through phosphorylation. The p38 family, a subfamily of MAPKs, plays a crucial role in regulating various cellular functions such as DNA repair and cell survival. Additionally, the balance of the BCL2 family members determines cell survival by controlling apoptosis signaling pathways.
Protein signaling networks are formed from diverse and inter-connected cell signaling pathways converging into webs of function and regulation. These signaling pathways both receive and conduct molecular messages, often by a series of post-translation modifications such as phosphorylation or through protein-protein interactions via intrinsic motifs. The mitogen activated protein kinases (MAPKs) are components of kinase cascades that transmit signals through phosphorylation. There are several MAPK subfamilies, and one subfamily is the stress-activated protein kinases, which in mammals is the p38 family. The p38 enzymes mediate a variety of cellular outcomes including DNA repair, cell survival/cell fate decisions, and cell cycle arrest. The cell cycle is itself a signaling system that precisely controls DNA replication, chromosome segregation, and cellular division. Another indispensable cell function influenced by the p38 stress response is programmed cell death (apoptosis). As the regulators of cell survival, the BCL2 family of proteins and their dynamics are exquisitely sensitive to cell stress. The BCL2 family forms a protein-protein interaction network divided into anti-apoptotic and pro-apoptotic members, and the balance of binding between these two sides determines cell survival. Here, we discuss the intersections among the p38 MAPK, cell cycle, and apoptosis signaling pathways.
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