由MYC驱动的USP39的激活增强了SRSF1的稳定性,并促进了PDAC的发展
bioRxiv : the preprint server for biology
|September 5, 2025
概括
研究人员在胰腺癌中发现了一种新的调节途径,涉及MYC,USP39和SRSF1. 这一轴稳定关键蛋白质,促进瘤生长,并为胰腺管腺癌提供潜在的新治疗点.
科学领域:
- 癌症学
- 分子生物学
- 癌症研究
背景情况:
- 胰腺管腺癌 (PDAC) 是一种由KRAS信号驱动的致命癌症.
- 剪接因子SRSF1在PDAC中至关重要,其表达水平影响瘤发生.
- SRSF1调节涉及蛋白质稳定,但具体机制尚未完全理解.
研究的目的:
- 在PDAC中确定调节SRSF1稳定的二基因酶.
- 阐明在胰腺癌中控制SRSF1的调节机制.
- 研究USP39作为PDAC的潜在治疗点.
主要方法:
- 确定USP39是一种SRSF1相互作用的二基因酶.
- 在PDAC瘤和患者生存数据中评估USP39表达.
- 在PDAC细胞中进行USP39淘汰和SRSF1过度表达实验.
- 调查了MYC对USP39的转录调节.
主要成果:
- 通过减少其无处不在,USP39稳定了SRSF1.
- USP39在PDAC上升调节,并与预后不佳相关.
- 抑制PDAC细胞的增殖和迁移.
- MYC通过其外体1b促进体直接激活USP39的转录.
结论:
- 一个MYC-USP39-SRSF1调控轴在PDAC中集成了转录和后翻译控制.
- USP39稳定了SRSF1,有助于KRAS驱动的PDAC.
- USP39是胰腺癌的一个有前途的治疗点.
相关概念视频
Abnormal Proliferation
4.6K
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...
4.6K
Anaphase Promoting Complex
2.9K
The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
2.9K
mTOR Signaling and Cancer Progression
3.9K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.9K
DNA Damage can Stall the Cell Cycle
9.3K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.3K
Inhibition of Cdk Activity
4.9K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.9K
PI3K/mTOR/AKT Signaling Pathway
3.9K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.9K


