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  1. Article ; Online: Phase separation driven by interchangeable properties in the intrinsically disordered regions of protein paralogs

    Shih-Hui Chiu / Wen-Lin Ho / Yung-Chen Sun / Jean-Cheng Kuo / Jie-rong Huang

    Communications Biology, Vol 5, Iss 1, Pp 1-

    2022  Volume 12

    Abstract: A comparison of structure-function relationship for intrinsically disordered regions (IDRs) among paralogs shows that differences in physicochemical properties of the IDR between paralogs are compensated for to converge on the same biophysical function. ...

    Abstract A comparison of structure-function relationship for intrinsically disordered regions (IDRs) among paralogs shows that differences in physicochemical properties of the IDR between paralogs are compensated for to converge on the same biophysical function.
    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2022-04-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Snail Augments Nuclear Deformability to Promote Lymph Node Metastasis of Head and Neck Squamous Cell Carcinoma

    Yin-Quan Chen / Chen-Yu Hung / Ming-Tzo Wei / Jean-Cheng Kuo / Muh-Hwa Yang / Han-Ying Cheng / Arthur Chiou

    Frontiers in Cell and Developmental Biology, Vol

    2022  Volume 10

    Abstract: Up to 50% of head and neck squamous cell carcinoma (HNSCC) patients have lymph node (LN) metastasis, resulting in poor survival rate. Numerous studies have supported the notion that the alterations of gene expression and mechanical properties of cancer ... ...

    Abstract Up to 50% of head and neck squamous cell carcinoma (HNSCC) patients have lymph node (LN) metastasis, resulting in poor survival rate. Numerous studies have supported the notion that the alterations of gene expression and mechanical properties of cancer cells play an important role in cancer metastasis. However, which genes and how they regulate the biomechanical properties of HNSCC cells to promote LN metastasis remains elusive. In this study, we used an LN-metastatic mouse model in vivo to generate an LN-metastatic head and neck squamous cell carcinoma cell line and compared the differences in the biomolecular and biomechanical properties of LN-metastatic and non-metastatic cells. Our results showed that LN-metastatic cells had a higher level of Snail expression compared to non-LN-metastatic cells. The higher Snail expression promoted the cellular invasion capability in confined environments, mainly by increasing the longitudinal strain of the cell nuclei, which could be attributed to the stronger cell traction force and softer nuclear stiffness. These two biomechanical changes were correlated, respectively, to a larger amount of focal adhesion and less amount of nuclear lamins. Taken together, our works revealed not only the biomechanical profiles of LN-metastatic cells but also the corresponding biomolecular expressions to pinpoint the key process in LN metastasis.
    Keywords lymph node metastasis ; snail ; cell mechanics ; invasion ; nuclear strain ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2022-02-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Development of vessel mimicking microfluidic device for studying mechano-response of endothelial cells

    Pei-Yu Chu / Han-Yun Hsieh / Pei-Shan Chung / Pai-Wen Wang / Ming-Chung Wu / Yin-Quan Chen / Jean-Cheng Kuo / Yu-Jui Fan

    iScience, Vol 26, Iss 6, Pp 106927- (2023)

    2023  

    Abstract: Summary: The objective of this study is to develop a device to mimic a microfluidic system of human arterial blood vessels. The device combines fluid shear stress (FSS) and cyclic stretch (CS), which are resulting from blood flow and blood pressure, ... ...

    Abstract Summary: The objective of this study is to develop a device to mimic a microfluidic system of human arterial blood vessels. The device combines fluid shear stress (FSS) and cyclic stretch (CS), which are resulting from blood flow and blood pressure, respectively. The device can reveal real-time observation of dynamic morphological change of cells in different flow fields (continuous flow, reciprocating flow and pulsatile flow) and stretch. We observe the effects of FSS and CS on endothelial cells (ECs), including ECs align their cytoskeleton proteins with the fluid flow direction and paxillin redistribution to the cell periphery or the end of stress fibers. Thus, understanding the morphological and functional changes of endothelial cells on physical stimuli can help us to prevent and improve the treatment of cardiovascular diseases.
    Keywords Cardiovascular medicine ; Biodevices ; Bioengineering ; Science ; Q
    Language English
    Publishing date 2023-06-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Liquid-liquid phase separation and extracellular multivalent interactions in the tale of galectin-3

    Yi-Ping Chiu / Yung-Chen Sun / De-Chen Qiu / Yu-Hao Lin / Yin-Quan Chen / Jean-Cheng Kuo / Jie-rong Huang

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 12

    Abstract: Galectin-3 consists of an unstructured N-terminal domain (NTD) and a structured carbohydrate-recognition domain and agglutinates neutrophils and glycosylated molecules in the extracellular milieu. Here the authors combine biophysical and biochemical ... ...

    Abstract Galectin-3 consists of an unstructured N-terminal domain (NTD) and a structured carbohydrate-recognition domain and agglutinates neutrophils and glycosylated molecules in the extracellular milieu. Here the authors combine biophysical and biochemical experiments with NMR measurements and show that the galectin-3 NTD undergoes liquid-liquid phase separation (LLPS) and agglutinates other molecules through this process.
    Keywords Science ; Q
    Language English
    Publishing date 2020-03-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Morphological and Molecular Defects in Human Three-Dimensional Retinal Organoid Model of X-Linked Juvenile Retinoschisis

    Kang-Chieh Huang / Mong-Lien Wang / Shih-Jen Chen / Jean-Cheng Kuo / Won-Jing Wang / Phan Nguyen Nhi Nguyen / Karl J. Wahlin / Jyh-Feng Lu / Audrey A. Tran / Michael Shi / Yueh Chien / Aliaksandr A. Yarmishyn / Ping-Hsing Tsai / Tien-Chun Yang / Wann-Neng Jane / Chia-Ching Chang / Chi-Hsien Peng / Thorsten M. Schlaeger / Shih-Hwa Chiou

    Stem Cell Reports, Vol 13, Iss 5, Pp 906-

    2019  Volume 923

    Abstract: Summary: X-linked juvenile retinoschisis (XLRS), linked to mutations in the RS1 gene, is a degenerative retinopathy with a retinal splitting phenotype. We generated human induced pluripotent stem cells (hiPSCs) from patients to study XLRS in a 3D retinal ...

    Abstract Summary: X-linked juvenile retinoschisis (XLRS), linked to mutations in the RS1 gene, is a degenerative retinopathy with a retinal splitting phenotype. We generated human induced pluripotent stem cells (hiPSCs) from patients to study XLRS in a 3D retinal organoid in vitro differentiation system. This model recapitulates key features of XLRS including retinal splitting, defective retinoschisin production, outer-segment defects, abnormal paxillin turnover, and impaired ER-Golgi transportation. RS1 mutation also affects the development of photoreceptor sensory cilia and results in altered expression of other retinopathy-associated genes. CRISPR/Cas9 correction of the disease-associated C625T mutation normalizes the splitting phenotype, outer-segment defects, paxillin dynamics, ciliary marker expression, and transcriptome profiles. Likewise, mutating RS1 in control hiPSCs produces the disease-associated phenotypes. Finally, we show that the C625T mutation can be repaired precisely and efficiently using a base-editing approach. Taken together, our data establish 3D organoids as a valid disease model. : Chiou, Schlaeger, and colleagues use hiPSC-derived retinal organoids to model X-linked juvenile retinoschisis. They show that patient hiPSC-derived retinal organoids replicate key pathologies observed in patients, including retinal splitting and photoreceptor deficit. The observed abnormalities were normalized in organoids derived from isogenic CRISPR/Cas9 gene-corrected hiPSCs. This validated XLRS in vitro model could be used to test and optimize therapeutic approaches. Keywords: retinal degeneration, X-linked juvenile retinoschisis, retinal organoid, induced pluripotent stem cells, retinogenesis, CRISPR/Cas9 gene editing, RS1, retinoschisin
    Keywords Medicine (General) ; R5-920 ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2019-11-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article: K33-Linked Polyubiquitination of Coronin 7 by Cul3-KLHL20 Ubiquitin E3 Ligase Regulates Protein Trafficking

    Yuan, Wei-Chien / Cheng-Hsin Liu / Chin-Chun Hung / Jean-Cheng Kuo / Li-Ying Chang / Mei-Yao Lin / Ming Xu / Ruey-Hwa Chen / Shu-Yu Lin / Yen Pei Tan / Yu-Ru Lee / Zhijian J. Chen

    Molecular cell. 2014 May 22, v. 54

    2014  

    Abstract: Ubiquitin chains are formed as structurally distinct polymers via different linkages, and several chain types including K33-linkage remain uncharacterized. Here, we describe a role for K33-polyubiquitination in protein trafficking. We show that the ... ...

    Abstract Ubiquitin chains are formed as structurally distinct polymers via different linkages, and several chain types including K33-linkage remain uncharacterized. Here, we describe a role for K33-polyubiquitination in protein trafficking. We show that the Cullin 3 (Cul3) substrate adaptor KLHL20 is localized to the trans-Golgi network (TGN) and is important for post-Golgi trafficking by promoting the biogenesis of TGN-derived transport carriers. The Cul3-KLHL20 ubiquitin E3 ligase catalyzes a nondegradable, K33-linked polyubiquitination on coronin 7 (Crn7), which facilitates Crn7 targeting to TGN through a ubiquitin-dependent interaction with Eps15. Blockage of K33-chain formation, Crn7 ubiquitination, or disruption of Crn7-Eps15 interaction impairs TGN-pool F-actin assembly, a process essential for generating transport carriers. Enforced targeting of Crn7 to TGN bypasses the requirement of K33-ubiquitination for TGN-pool F-actin assembly and post-Golgi trafficking. Our study reveals a role of KLHL20-mediated K33-ubiquitination of Crn7 in post-Golgi transport and identifies a cellular recognition mechanism for this ubiquitin chain type.
    Keywords actin ; biogenesis ; polymers ; protein transport ; ubiquitin ; ubiquitination ; ubiquitin-protein ligase
    Language English
    Dates of publication 2014-0522
    Size p. 586-600.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 1415236-8
    ISSN 1097-4164 ; 1097-2765
    ISSN (online) 1097-4164
    ISSN 1097-2765
    DOI 10.1016/j.molcel.2014.03.035
    Database NAL-Catalogue (AGRICOLA)

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