Recently, researchers from the Second Military Medical University, Jilin University and other institutions have revealed a new signaling mechanism for integrin-linked kinase-related phosphatase (ILKAP) to regulate cell survival and apoptosis. Professor Jianru Xiao and Professor Tielong Liu of the Second Military Medical University are co-corresponding authors of this article. The former is mainly engaged in basic clinical research on spinal tumors and spinal injuries. The latter has long been engaged in clinical work of spinal surgery and related research. Integrin-linked kinase-related phosphatase (ILKAP) is a new member of the protein phosphatase 2C (PP2C) family. Although the international understanding of it is still very limited, preliminary research results have shown that this is a kind of apoptosis Signal pathways are closely related to protein phosphatases. ILKAP is widely expressed in human tissues, with high levels of expression in skeletal muscle, kidney and liver. Mediating apoptosis is the main physiological function of ILKAP, and therefore has a close relationship with the occurrence and development of tumors and other diseases. Some studies have shown that ILKAP may play a role by negatively regulating integrin kinase signaling pathway and positively regulating c-Jun amino terminal kinase / mitogen-activated protein kinase (JNK / MAPK) signaling pathway. In previous studies, it was confirmed that ILKAP negatively regulates integrin protein signaling through interaction with phosphorylated integrin-linked kinase 1 (ILK1), and suggests that ILKAP may be a cytoplasmic protein. In this article, the researchers found that both endogenous and labeled ILKAP are mainly localized in the nucleus, and the nuclear localization signal (NLS) importin importin mediates ILKAP nuclear transport. ILKAP directly interacts with importin α1, α3 and α5. The researchers confirmed that the NLS of ILKAP is located between amino acids 71-86 in the N-terminal region. When they knocked out the NLS of the ILKAP protein, they found that it caused ILKAP to localize in the cytoplasm. They confirmed that Lys-78 and Arg-79 are essential for ILKAP binding to importinα. In addition, the researchers also found that nuclear ILKAP interacted with the ribosomal S6 kinase RSK2. By inhibiting RSK2 activity, it down-regulated the level of cyclin D1, a downstream substrate of RSK2, and induced apoptosis. These results indicate that ILKAP can be nuclearly transported by importin, and regulate cell survival and apoptosis by regulating RSK2 signaling in the nucleus. Track Lighting Systems Led,Good Quality Led Downlights,Led Ceiling Strip Light Fittings Jilin Province Yuaoda Trading Co., Ltd , https://www.yuaodacn.com
Research reveals apoptosis signaling mechanism