在三阴性乳腺癌中,SDCBP/Syntenin-1通过分解SCFFBXO22-BACH1复合体来稳定BACH1
Phi-Long Tran1, Okhwa Kim2, Cheol Hwangbo3
1Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon-si, Gangwon-do, 24341, Republic of Korea.
The EMBO journal
|April 22, 2025
概括
通过防止其降解,SDCBP稳定了三阴性乳腺癌 (TNBC) 中的BACH1蛋白. 这种相互作用抑制了瘤的进展,并增强了甲福林的作用.
科学领域:
- 分子瘤学分子瘤学
- 癌症生物学 癌症生物学
- 生物化学 生物化学
背景情况:
- BACH1是推动三阴性乳腺癌 (TNBC) 进展的关键转录因子.
- 控制TNBC中BACH1稳定性和功能的精确机制尚未完全理解.
研究的目的:
- 阐明调节TNBC中BACH1稳定性的分子机制.
- 研究SDCBP在控制BACH1稳定性的作用及其对TNBC进展和治疗反应的影响.
主要方法:
- 使用TNBC细胞系研究了SDCBP和BACH1之间的相互作用.
- 在TNBC患者组织中分析了SDCBP和BACH1表达相关性.
- 对SDCBP进行了淘汰性研究,以评估其对BACH1降解,基因表达和瘤进展的影响.
- 评估了SDCBP枯竭对线粒体活性和甲胺疗效的影响.
主要成果:
- 在TNBC细胞中,SDCBP稳定了BACH1,通过防止其无处化和蛋白质体降解,独立于血质.
- 在TNBC中,SDCBP和BACH1表达是正相关的.
- SDCBP的敲击抑制了瘤的进展,并调节了BACH1-抑制的电子运输链 (ETC) 基因,增强了甲胺的抗瘤作用.
- SDCBP的PDZ1域对于拆解SCF-BACH1复合体至关重要.
结论:
- 通过一种新的机制,SDCBP稳定了TNBC中的BACH1,防止其降解.
- SDCBP-BACH1轴代表了一个潜在的治疗点,以提高ETC抑制剂在TNBC治疗中的疗效.
相关概念视频
The Spindle Assembly Checkpoint
3.1K
The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
3.1K
Destabilization of Microtubules
2.5K
The destabilization of microtubules can occur during different stages of the microtubule lifecycle, such as nucleation or elongation. It can take place at either end of the microtubule or in the microtubule lattices as a whole. The lifespan of individual microtubules within a cell varies according to the cell type and stage of the cell cycle. During interphase, the lifespan of the microtubule is about 30 minutes, while during cell division, it is about 15 minutes. In axonal microtubules of...
2.5K
Separation of Sister Chromatids
3.5K
At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
At the onset of anaphase, separase, a proteolytic enzyme, is...
At the onset of anaphase, separase, a proteolytic enzyme, is...
3.5K
Microtubule Instability
4.9K
Microtubules are hollow cylindrical filaments having a diameter of approximately 25 nm and a length that varies from 200 nm to 25 μm. GTP-bound tubulin subunits form αβ-heterodimers for microtubule assembly. These core building blocks interact longitudinally, polymerizing into protofilaments. The protofilaments then interact with one another through lateral bonding forces to form stable cylindrical microtubules. These cylindrical filaments are dynamic as they undergo repeated...
4.9K
Restarting Stalled Replication Forks
5.7K
DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
5.7K
Disassembly of Intermediate Filaments
2.0K
Intermediate filaments (IFs) do not undergo spontaneous disassembly. Enzymes, kinases, and phosphatases add and remove phosphates from specific sites to regulate their disassembly. The IF concentration in the cytoplasm also regulates the disassembly. If the concentration crosses a threshold, it activates the protein kinases in the vicinity, allowing the phosphorylation of IFs.
Keratin proteins, found at the cell periphery near cell junctions, undergo a cycle of assembly and disassembly. In Type...
Keratin proteins, found at the cell periphery near cell junctions, undergo a cycle of assembly and disassembly. In Type...
2.0K


