调节ALKBH1的丰度和基质特异性,以促进翻译和瘤性
Emma Wilkinson1, Yan-Hong Cui2, Zizhao Yang2
1Department of Medicine, Section of Dermatology, The University of Chicago, Chicago, IL, USA; Committee on Cancer Biology, The University of Chicago, Chicago, IL, USA.
Cell reports
|October 5, 2025
概括
通过改变ALKBH1活动,从而影响RNA甲基化,促进皮肤癌. 向ALKBH1可以提供针对诱导瘤发生的新策略.
科学领域:
- 环境毒理学环境毒理学
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 在瘤形成中的作用尚未完全理解.
- 关联暴露与癌症的分子机制需要进一步阐明.
研究的目的:
- 研究ALKBH1在引起的皮肤瘤发生中的作用.
- 揭示如何影响ALKBH1活动和下游目标的分子机制.
主要方法:
- 在暴露于的角质细胞中研究了ALKBH1的丰度和脱甲基酶活性.
- 使用m6A-免疫沉 (IP) 测序来识别ALKBH1标.
- 研究了ALKBH1调制对NR2C2表达和mTOR信号传递的影响.
主要成果:
- 调节ALKBH1的丰富性和脱甲基酶活性,促进皮肤瘤发生.
- ALKBH1以一种依赖的方式直接去甲基化m6A,影响NR2C2转化.
- 抑制ALKBH1导致NR2C2表达的增加,mTOR激活的减少和全球翻译的减少.
结论:
- 与ALKBH1氨酸残留物的结合调节其m6A脱甲基酶活性.
- ALKBH1是诱导瘤发生的关键媒介,影响NR2C2翻译和mTOR信号传递.
- ALKBH1代表了一种潜在的可药物剂标和相关癌症的生物标志物.
相关概念视频
Allosteric Proteins-ATCase
6.5K
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
6.5K
Leaky Scanning
5.6K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.6K
Abnormal Proliferation
5.1K
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...
5.1K
Covalently Linked Protein Regulators
8.7K
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....
8.7K
Regulation of Expression at Multiple Steps
1.3K
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
1.3K
mTOR Signaling and Cancer Progression
4.6K
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...
4.6K


