FOXK1的O-GlcNAcylation选择了BAP1来协调E2F通路,并促进了瘤发生
Oumaima Ahmed1, Louis Masclef1, Nicholas Iannantuono2
1Centre de recherche de l'Hôpital Maisonneuve-Rosemont, CIUSSS de l'Est-de-l'Ȋle de Montréal, Montréal, QC, Canada.
Nature communications
|July 2, 2025
概括
转录因子FOXK1通过增强E2F目标基因来促进癌症. 它的O-GlcNAcylation修饰对于招募瘤抑制剂BAP1至关重要,以调节细胞增殖和瘤生长.
科学领域:
- 分子生物学分子生物学
- 在瘤学瘤学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- E2F转录因子调节细胞分裂和瘤发生.
- 控制E2F活动的精确分子机制尚未完全理解.
研究的目的:
- 研究FOXK1在E2F介导的瘤发生中的作用.
- 阐明FOXK1影响细胞增殖和瘤生长的分子机制.
主要方法:
- 对患者瘤中的FOXK1表达的分析.
- 对FOXK1 O-GlcNAcylation的研究.
- 评估BAP1对E2F目标基因的招募.
- 在对FOXK1修饰的反应中评估细胞增殖和瘤生长.
主要成果:
- 增加的FOXK1表达与增加的E2F基因转录和细胞转化相关.
- FOXK1 O-GlcNAcylation对于促进细胞增殖和瘤生长至关重要.
- 失去FOXK1 O-GlcNAcylation会影响BAP1对E2F目标基因的招募,从而导致扩散的减少.
结论:
- 通过协调E2F通路,FOXK1在癌症进展中发挥着关键作用.
- FOXK1 O-GlcNAcylation 是一个关键的调节机制,它选择了瘤抑制剂BAP1来促进癌症.
- 向FOXK1 O-GlcNAcylation可能为癌症治疗提供一种新的治疗策略.
相关概念视频
PI3K/mTOR/AKT Signaling Pathway
4.0K
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...
4.0K
MAPK Signaling Cascades
6.2K
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...
6.2K
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
The Ras Gene
6.5K
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
Ras is a...
6.5K
Interactions Between Signaling Pathways
6.6K
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...
6.6K
The Intrinsic Apoptotic Pathway
6.9K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.9K


