在结肠癌中,维生素D通过K610脱乙来诱导SIRT1的激活
José Manuel García-Martínez1, Ana Chocarro-Calvo1, Javier Martínez-Useros1,2
1Area of Physiology, Faculty Health Sciences, University Rey Juan Carlos, Alcorcón, Madrid, Spain.
eLife
|August 2, 2023
概括
活性维生素D代谢物 (calcitriol) 通过促进自脱乙烯化,在结肠癌细胞中激活SIRT1. 这种SIRT1激活调解了维生素D的抗癌作用,提供了潜在的新疗法.
科学领域:
- 表观遗传学和分子生物学
- 癌症研究 癌症研究
- 内分泌学 在内分泌学.
背景情况:
- 翻译后修改调节表观遗传修饰剂,使癌细胞适应.
- SIRT1,一种依赖NAD+的表观遗传修饰剂,尽管与衰老有关,但在癌症中其作用尚不清楚.
研究的目的:
- 为了研究SIRT1在结肠癌中的作用.
- 阐明维生素D代谢物影响SIRT1活性的机制.
- 探索向SIRT1在结肠癌中的治疗潜力.
主要方法:
- 研究了1α,25-二氧维生素D3 (1,25(OH) 2D3对人类结肠癌细胞中SIRT1活性的影响.
- 确定了参与SIRT1自脱乙和活性的关键残留物.
- 评估了1,25(OH) 2D3和SIRT1激活剂的抗增殖作用.
主要成果:
- 1,25(OH) 2D3通过在结肠癌细胞中的自脱乙化来激活SIRT1.
- 氨酸610对于SIRT1活动至关重要.
- 通过1,25(OH) 2D3激活SIRT1调解其抗增殖作用;SRT1720模仿这种作用.
结论:
- 通过1,25(OH) 2D3对SIRT1的翻译后调节是结肠癌的一个关键机制.
- 像SRT1720这样的SIRT1激活剂可能为缺乏维生素D或不响应结肠癌患者提供治疗效益.
- 这些发现可能会扩展到与维生素D缺乏和炎症相关的其他流行疾病,其中SIRT1涉及.
相关概念视频
01:23Role of Skin in Vitamin D Synthesis
5.3K
The skin plays a crucial role in the synthesis of vitamin D, a vital nutrient for various physiological processes in the body. Vitamin D is unique because it can be synthesized in the skin through a series of chemical reactions triggered by exposure to ultraviolet B (UVB) radiation from sunlight.
The solar UV B rays (290-315 nm) are absorbed by the skin, and 7-dehydrocholesterol (provitamin D3) photolyzes it to previtamin D3, which undergoes a rapid transformation to vitamin...
The solar UV B rays (290-315 nm) are absorbed by the skin, and 7-dehydrocholesterol (provitamin D3) photolyzes it to previtamin D3, which undergoes a rapid transformation to vitamin...
5.3K
03:03mTOR Signaling and Cancer Progression
3.8K
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...
3.8K
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
2.1K
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.1K
01:22PI3K/mTOR/AKT Signaling Pathway
3.7K
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...
3.7K
02:04Covalently Linked Protein Regulators
6.9K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
6.9K