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Histone variants: critical determinants in tumour heterogeneity

Tao Wang, Florent Chuffart, Ekaterina Bourova-Flin, Jin Wang, Jianqing Mi, Sophie Rousseaux, Saadi Khochbin

《医学前沿（英文）》 2019年第13卷第3期页码 289-297 doi: 10.1007/s11684-018-0667-3

摘要： Malignant cell transformation could be considered as a series of cell reprogramming events driven by oncogenic transcription factors and upstream signalling pathways. Chromatin plasticity and dynamics are critical determinants in the control of cell reprograming. An increase in chromatin dynamics could therefore constitute an essential step in driving oncogenesis and in generating tumour cell heterogeneity, which is indispensable for the selection of aggressive properties, including the ability of cells to disseminate and acquire resistance to treatments. Histone supply and dosage, as well as histone variants, are the best-known regulators of chromatin dynamics. By facilitating cell reprogramming, histone under-dosage and histone variants should also be crucial in cell transformation and tumour metastasis. Here we summarize and discuss our knowledge of the role of histone supply and histone variants in chromatin dynamics and their ability to enhance oncogenic cell reprogramming and tumour heterogeneity.

关键词： cancer-testis TH2B TH2A H1T H1.0 H1F0 linker histones

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A dual-function chemical probe for detecting erasers of lysine lipoylation

Yusheng Xie, Jie Zhang, Liu Yang, Qingxin Chen, Quan Hao, Liang Zhang, Hongyan Sun

《化学科学与工程前沿（英文）》 2022年第16卷第1期页码 121-127 doi: 10.1007/s11705-021-2051-0

摘要： Lysine lipoylation plays vital roles in cell metabolism and redox processes. For example, removal of lipoylation will decrease pyruvate dehydrogenase activity and affect the citric acid cycle. Despite the important functions of lysine lipoylation, the mechanisms for the addition and removal of this modification remain largely unexplored. Very few useful chemical tools are available to study the interactions of lysine lipoylation with its regulatory delipoylation proteins. For example, immunoaffinity purification-mass spectrometry is one of such tools, which highly relies on antibody efficiency and purification techniques. Single-step activity based fluorogenic probes developed by our groups and others is also an efficient method to study the deacylation activity. Affinity-based labeling probe using photo-cross-linker is a powerful platform to study the transient and dynamic interactions of peptide ligands with the interacting proteins. Herein, we have designed and synthesized a dual-function probe KTLlip for studying enzymatic delipoylation (eraser) activity and interaction of lysine lipoylation with the eraser at the same time. We show that KTLlip can be used as a useful tool to detect delipoylation as demonstrated by its ability to fluorescently label the eraser activity of recombinant Sirt2. We envision that the probe will help delineate the roles of delipoylation enzyme in biology.

关键词： dual-function fluorescent probe labeling photo-cross-linker lipoylation modification eraser sirtuin