Material properties of phase-separated TFEB condensates regulate the autophagy-lysosome pathway DOI Creative Commons

Zheng Wang,

Di Chen, Dongshi Guan

и другие.

The Journal of Cell Biology, Год журнала: 2022, Номер 221(5)

Опубликована: Март 16, 2022

Very little is known about how the material properties of protein condensates assembled via liquid–liquid phase separation (LLPS) are maintained and affect physiological functions. Here we show that liquid-like transcription factor TFEB exhibit low fusion propensity in vitro living cells. We directly measured attraction force between droplets, characterized interfacial tension, viscosity, elasticity condensates. contain rigid boundaries govern their interaction behaviors. Several small molecules, including Ro-3306, modify condensates, increasing size propensity. These compounds promote lysosomal biogenesis function a TFEB-dependent manner without changing its cytoplasmic-nuclear translocation. Ro-3306 promotes autophagy activity, facilitating degradation toxic aggregates. Our study helps explain as physically separate entities reveals can be harnessed to modulate activity.

Язык: Английский

Biological roles and therapeutic potential of circular RNAs in osteoarthritis DOI Creative Commons

Xingjia Mao,

Yanyan Cao, Zijian Guo

и другие.

Molecular Therapy — Nucleic Acids, Год журнала: 2021, Номер 24, С. 856 - 867

Опубликована: Май 8, 2021

Osteoarthritis (OA) is a common and disabling joint disorder that mainly characterized by cartilage degeneration narrow spaces. The regulatory functions of non-coding RNAs (long RNAs, microRNAs [miRNAs], circular [circRNAs]) in OA progression have attracted considerable attention, the function context has been an increasingly popular research topic last 6 years. Recent studies reported various circRNAs can delay or aggravate diverse aspects process, including extracellular matrix formation, apoptosis, proliferation, inflammation, autophagy, via circRNA/miRNA/mRNA pathways. Thus, related pathways are potential therapeutic targets for OA. Our review provides comprehensive information about circRNAs, their biogenesis, functions, characteristics, it reveals critical roles pathogenesis large network sponges. Considering we hypothesize not only be transferred through bodily fluids to serve as diagnostic biomarkers, but they also released from mesenchymal stem cell-derived exosomes delivered chondrocytes acting circRNAs. Further investigations in-depth molecular mechanisms action expected provide effective safe treatment strategies.Graphical abstract

Язык: Английский

Процитировано

46
YB-1 as an Oncoprotein: Functions, Regulation, Post-Translational Modifications, and Targeted Therapy DOI Creative Commons

Qiyan Yin,

Min Zheng,

Qianmei Luo

и другие.

Cells, Год журнала: 2022, Номер 11(7), С. 1217 - 1217

Опубликована: Апрель 4, 2022

Y box binding protein 1 (YB-1) is a with highly conserved cold shock domain (CSD) that also belongs to the family of DNA- and RNA-binding proteins. YB-1 present in both nucleus cytoplasm plays versatile roles gene transcription, RNA splicing, DNA damage repair, cell cycle progression, immunity. Cumulative evidence suggests promotes progression multiple tumor types serves as potential biomarker therapeutic target. This review comprehensively summarizes emerging functions, mechanisms, regulation cancers, further discusses targeted strategies.

Язык: Английский

Процитировано

38
LC3-associated endocytosis and the functions of Rubicon and ATG16L1 DOI Creative Commons
Joëlle Magné, Douglas R. Green

Science Advances, Год журнала: 2022, Номер 8(43)

Опубликована: Окт. 26, 2022

LC3-associated endocytosis (LANDO) is a noncanonical function of the autophagy machinery, in which LC3 (microtubule-associated protein light chain) conjugated to rab5-positive endosomes, using portion canonical pathway. LANDO was initially discovered murine model Alzheimer's disease as critical regulator amyloid-β receptor recycling microglial cells, playing protective role against neuronal loss and memory impairment. Recent evidence suggests an emerging cytokine signaling innate immunity. Here, we discuss regulation two crucial effectors LANDO, Rubicon ATG16L1, their impact on endocytosis, autophagy, phagocytosis.

Язык: Английский

Процитировано

37
How do protein aggregates escape quality control in neurodegeneration? DOI
Margreet B. Koopman, Luca Ferrari, Stefan Rüdiger

и другие.

Trends in Neurosciences, Год журнала: 2022, Номер 45(4), С. 257 - 271

Опубликована: Фев. 21, 2022

Язык: Английский

Процитировано

35
Material properties of phase-separated TFEB condensates regulate the autophagy-lysosome pathway DOI Creative Commons

Zheng Wang,

Di Chen, Dongshi Guan

и другие.

The Journal of Cell Biology, Год журнала: 2022, Номер 221(5)

Опубликована: Март 16, 2022

Very little is known about how the material properties of protein condensates assembled via liquid–liquid phase separation (LLPS) are maintained and affect physiological functions. Here we show that liquid-like transcription factor TFEB exhibit low fusion propensity in vitro living cells. We directly measured attraction force between droplets, characterized interfacial tension, viscosity, elasticity condensates. contain rigid boundaries govern their interaction behaviors. Several small molecules, including Ro-3306, modify condensates, increasing size propensity. These compounds promote lysosomal biogenesis function a TFEB-dependent manner without changing its cytoplasmic-nuclear translocation. Ro-3306 promotes autophagy activity, facilitating degradation toxic aggregates. Our study helps explain as physically separate entities reveals can be harnessed to modulate activity.

Язык: Английский

Процитировано

35