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2023年11月嘲风作品集（二）

已有 1314 次阅读 2024-1-25 14:26 |个人分类:作品发表|系统分类:论文交流

▲ Vol 83 Issue 21 | November 02, 2023

TAK1 is an essential kinase for STING trafficking

Mingtong Ma, Yifang Dang, Boran Chang, Fei Wang, Junfang Xu, Li Chen, Hang Su, Jinsong Li, Baoxue Ge, Chang Chen, Haipeng Liu

The translocation of stimulator of interferon genes (STING) from the endoplasmic reticulum (ER) to the ER–Golgi intermediate compartment (ERGIC) enables its activation. However, the mechanism underlying the regulation of STING exit from the ER remains elusive. Here, we found that STING induces the activation of transforming growth factor beta-activated kinase 1 (TAK1) prior to STING trafficking in a TAK1 binding protein 1 (TAB1)-dependent manner. Intriguingly, activated TAK1 directly mediates STING phosphorylation on serine 355, which facilitates its interaction with STING ER exit protein (STEEP) and thereby promotes its oligomerization and translocation to the ERGIC for subsequent activation. Importantly, activation of TAK1 by monophosphoryl lipid A, a TLR4 agonist, boosts cGAMP-induced antitumor immunity dependent on STING phosphorylation in a mouse allograft tumor model. Taken together, TAK1 was identified as a checkpoint for STING activation by promoting its trafficking, providing a basis for combinatory tumor immunotherapy and intervention in STING-related diseases.

https://www.cell.com/molecular-cell/fulltext/S1097-2765(23)00704-9‍

▲ Vol 123 Issue 21 | November 08, 2023

Advanced Techniques for Detecting Protein Misfolding and Aggregation in Cellular Environments

Yulong Bai, Shengnan Zhang, Hui Dong, Yu Liu, Cong Liu, and Xin Zhang

Protein misfolding and aggregation, a key contributor to the progression of numerous neurodegenerative diseases, results in functional deficiencies and the creation of harmful intermediates. Detailed visualization of this misfolding process is of paramount importance for improving our understanding of disease mechanisms and for the development of potential therapeutic strategies. While in vitro studies using purified proteins have been instrumental in delivering significant insights into protein misfolding, the behavior of these proteins in the complex milieu of living cells often diverges significantly from such simplified environments. Biomedical imaging performed in cell provides cellular-level information with high physiological and pathological relevance, often surpassing the depth of information attainable through in vitro methods. This review highlights a variety of methodologies used to scrutinize protein misfolding within biological systems. This includes optical-based methods, strategies leaning on mass spectrometry, in-cell nuclear magnetic resonance, and cryo-electron microscopy. Recent advancements in these techniques have notably deepened our understanding of protein misfolding processes and the features of the resulting misfolded species within living cells. The progression in these fields promises to catalyze further breakthroughs in our comprehension of neurodegenerative disease mechanisms and potential therapeutic interventions.

https://pubs.acs.org/doi/10.1021/acs.chemrev.3c00494

▲ Vol 44 Issue 06 | November 20, 2023

薄层纸喷雾离子化-小型便携式质谱法即时检验血液中免疫抑制剂

谢以清, 郭项雨, 张文鹏, 欧阳证, 马强

以铝基硅胶薄层板作为纸喷雾离子源基底材料，结合小型便携式质谱建立了血液样品中他克莫司、西罗莫司、依维莫司、环孢素A和霉酚酸等5种免疫抑制剂的即时检验方法。将铝基硅胶薄层板剪成三角形，滴加10 μL血液样品，以20 μL甲醇作为洗脱/喷雾溶剂，薄层板尖端距离小型便携式质谱进样口1.0 cm，施加喷雾电压，样品在薄层板上洗脱后形成电喷雾，进入小型便携式质谱进行分析。结果表明，5种免疫抑制剂在各自的线性范围内呈现良好的线性关系，相关系数（r）为0.993 9~0.996 8，检出限和定量限分别为0.5~5、1~10 mg/L。在低、中、高3个加标浓度水平下，平均回收率在91.0%~114.3%之间，相对标准偏差（RSD）小于8.4%，检测周期小于1 min。该方法简单快速、准确高效，适用于血液中免疫抑制剂的即时床旁分析。

http://www.jcmss.com.cn/CN/10.7538/zpxb.2023.0063

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