ATR在核信封上进行了一次破解
Marcus B Smolka1, Jan Lammerding2
1Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA; Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
Molecular cell
|October 20, 2023
概括
通过酸化拉胺A/C,ATR激酶触发核膜破裂. 这一过程激活了cGAS-STING通路,清除了微核,并可能导致细胞死亡.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 核膜完整性对于细胞功能至关重要.
- 核过程的失调与各种疾病有关.
- ATR激酶在DNA损伤反应中发挥作用.
研究的目的:
- 为了研究ATR激酶在核外破裂中的作用.
- 为了确定ATR介导的核外破裂的下游影响因素.
- 探索核膜破裂在细胞过程中的影响.
主要方法:
- 西方涂抹检测蛋白质酸化.
- 免疫光显微镜可视化核结构.
- 细胞测试以评估途径激活和细胞死亡.
主要成果:
- 酸化ATR激酶Lamin A/C,这是核膜的一个关键组成部分.
- 通过ATR对Lamin A/C的酸化促进了核外破裂.
- 通过ATR介导的核外破裂会诱导cGAS-STING通路的激活和微核的清除.
结论:
- ATR激酶是核外破裂的关键调节者.
- 酸化拉胺A/C是ATR诱导核外破裂的关键机制.
- 由ATR介导的核膜破裂对细胞平衡和生存有着显著的下游影响.
相关概念视频
Nuclear Protein Sorting
4.6K
Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
4.6K
Nuclear Export
3.7K
The nucleus restricts several proteins within and allows others to pass. The restricted proteins possess a nuclear retention sequence or NRS, anchoring them to the nuclear lamins and preventing their transport to the cytosol. The non-restricted proteins, after their synthesis, are transported to their site of action, such as the cytosol or other organelles, with the help of nuclear export signals or NES.
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
3.7K
Regulation of Nuclear Protein Sorting
2.4K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
Directionality of Nuclear Transport
3.3K
Ras-related nuclear protein or Ran is a small G protein that cycles between its GTP and GDP bound states. Ran specific regulators, a Ran GTPase Activating Protein or RanGAP present in the cytosol and a Ran guanine nucleotide exchange factor or RanGEF present inside the nucleus regulate GTP/GDP exchange. A high concentration of GTP inside the cells, in addition to this asymmetric distribution of Ran-specific regulators, leads to a higher RanGTP concentration inside the nucleus. This...
3.3K
Cotranslational Protein Translocation
7.4K
Translocation of proteins across membranes is an ancient process that occurs even in bacteria and archaebacteria. In fact, the components of the translocation machinery are still conserved between prokaryotes and eukaryotes.
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain...
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain...
7.4K
Protein Translocation Machinery on the ER Membrane
4.6K
The translocon complex situated on the ER membrane is the main gateway for the protein secretory pathway. It facilitates the transport of nascent peptides into the ER lumen and their insertion into the ER membrane.
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the...
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the...
4.6K


