| 靶标 | HBV X-interacting protein, HBX-interacting protein, HBXIP, Hepatitis B virus X-interacting protein, LAMTOR5, Late endosomal/lysosomal adaptor and MAPK and MTOR activator 5, Ragulator complex protein LAMTOR5, XIP |
|---|
| 背景 | Ragulator complex protein LAMTOR5 (HBXIP) is a ~9 kDa protein. As part of the Ragulator complex it is involved in amino acid sensing and activation of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids. Activated by amino acids through a mechanism involving the lysosomal V-ATPase, the Ragulator plays a dual role for the small GTPases Rag (RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and/or RagD/RRAGD): it (1) acts as a guanine nucleotide exchange factor (GEF), activating the small GTPases Rag and (2) mediates recruitment of Rag GTPases to the lysosome membrane. Activated Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated. When complexed to BIRC5, interferes with apoptosome assembly, preventing recruitment of pro-caspase-9 to oligomerized APAF1, thereby selectively suppressing apoptosis initiated via the mitochondrial/cytochrome c pathway. 2. Yonehara, R. et al. (2017) Nature communications 8, 1625. PMID: 291584923. Shen, K. et al. (2018) Proceedings of the National Academy of Sciences of the United States of America 115, 9545-9550. PMID: 301812604. de Araujo, MEG. et al. (2017) Science (New York, N.Y.) 358, 377-381. PMID: 289357705. Su, MY. et al. (2017) Molecular cell 68, 835-846.e3. PMID: 29107538 |
|---|
