Gp93抑制了未折叠的蛋白质反应介导的c-Jun N-终端激酶激活和细胞入侵
Meng Xu1, Zhihan Wu1, Wenzhe Li1
1Institute of Intervention Vessel, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology, Tongji University, Shanghai, China.
Journal of cellular physiology
|June 26, 2024
概括
这项研究揭示了Drosophila Gp93,Hsp90B1的同源,通过JNK通路调节细胞入侵. 这一发现对Hsp90B1抑制剂癌症治疗有影响.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 发展生物学 发展生物学
背景情况:
- 热冲击蛋白90β1 (Hsp90B1) 是真核生物中至关重要的护卫蛋白,对于蛋白质折叠至关重要.
- Hsp90B1在癌症发育中表现出矛盾的作用,其机制在很大程度上是未知的.
- 在此之前,Gp93的发育功能,Hsp90B1的Drosophila Ortholog,是未被充分研究的.
研究的目的:
- 研究Drosophila Gp93在细胞过程中的功能作用.
- 阐明Gp93在细胞入侵中的功能背后的分子机制.
- 探索Gp93,JNK信号传递和展开的蛋白质反应 (UPR) 之间的联系.
主要方法:
- 使用了Drosophila模型系统.
- 使用Drosophila细胞入侵试验.
- 研究了 IRE1/XBP1 途径在 Gp93 枯竭诱导效应中的作用.
主要成果:
- Gp93在调节Drosophila的细胞入侵方面发挥着重要作用.
- Gp93调节了c-Jun N-终端激酶 (JNK) 的激活.
- 由Gp93耗尽引起的,依赖JNK的细胞入侵与IRE1/XBP1 UPR通路有关.
结论:
- 在Drosophila发育和细胞入侵中发现了Gp93的新型分子功能.
- 建立了Gp93,JNK信号传递和UPR通路之间的联系,以调节细胞入侵.
- 突出了基于Hsp90B1抑制剂的癌症治疗的潜在考虑因素.
相关概念视频
Abnormal Proliferation
4.5K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
Receptor Downregulation in MVBs
2.0K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.0K
The Unfolded Protein Response
4.5K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
4.5K
The JAK-STAT Signaling Pathway
8.8K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
8.8K
Interactions Between Signaling Pathways
6.3K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.3K
MAPK Signaling Cascades
5.4K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.4K


