Results 111 to 120 of about 225,633 (278)

Targeted Cell-to-Cell Delivery of Protein Payloads via the Granzyme-Perforin Pathway

Molecular Therapy: Methods & Clinical Development, 2017
There is great potential for engineering cellular therapeutics by repurposing biological systems. Here, we report utilization of the granzyme-perforin pathway of cytotoxic lymphocytes as a cell-to-cell protein delivery module. We designed and constructed
Daniel J. Woodsworth, Lisa Dreolini, Libin Abraham, Robert A. Holt   +3 more
doaj   +1 more source

Single‐Cell Atlas of Subchondral Bone Marrow Lesions Reveals Proteostasis Dysfunction as a Druggable Mechanism for Early Osteoarthritis

Advanced Science, EarlyView.
This study reveals that abnormal mechanical stress downregulates the expression of HSP70 and impairs proteasome function in osteoarthritic bone cells, leading to misfolded collagen I accumulation and ER stress. When intracellular proteostasis capacity is exceeded, USP19 mediates the secretion of misfolded proteins into the extracellular space ...
Hailun Xu, Ting He, Yu Qian, Jia Li, Bowei Ni, Xiaojie Xu, Huanbo Wang, Peng Wang, Guoqing Cao, Siqi Ying, Guangyu Ding, Rong Wang, Zenghui Gu, Wei Li, Zhentao Man, Houfeng Zheng, Zhaohua Zhu, Zhen Li, Qingjun Meng, Chao Zheng, Liu Yang   +20 more
wiley   +1 more source

Alphaviral Capsid Proteins Inhibit Stress Granule Assembly via Competitive RNA Binding With G3BP1

Advanced Science, EarlyView.
Stress granules exert antiviral functions. This study illustrates a conserved function of alphaviral capsid proteins in modulating stress granules. Oligomerization mediated by a helical motif coupled with a positively charged intrinsically disordered region (IDR) directly competes with G3BP1 for RNA binding, thereby disrupting G3BP1‐RNA liquid–liquid ...
Yun Zhang, Yi Liu, Zhiying Yao, Haolong Lai, Xiaoxin Chen, Ziqiu Wang, Yiqiong Bao, Tingting Li, Xiaoming Zhou, Xiabin Chen, Peiguo Yang   +10 more
wiley   +1 more source

Mutation of the co-chaperone Tsc1 in bladder cancer diminishes Hsp90 acetylation and reduces drug sensitivity and selectivity [PDF]

, 2019
The molecular chaperone Heat shock protein 90 (Hsp90) is essential for the folding, stability, and activity of several drivers of oncogenesis. Hsp90 inhibitors are currently under clinical evaluation for cancer treatment, however their efficacy is ...
Backe, Sarah J, Baker-Williams, Alexander J, Bourboulia, Dimitra, Bratslavsky, Gennady, Bratslavsky, Michael S, Hughes, Michael, Jacob, Joseph M, Mollapour, Mehdi, Sager, Rebecca A, Shapiro, Oleg, Wong, Michael, Woodford, Mark R   +11 more
core   +1 more source

Mitochondrial CircRNA CircMT‐RNR2 Safeguards Antioxidant Defense to Support Fibroblast Functions in Wound Repair

Advanced Science, EarlyView.
CircMT‐RNR2 promotes wound healing by enhancing fibroblast proliferation, migration, contraction, and extracellular matrix (ECM) production. It sustains mitochondrial redox balance by stabilizing the antioxidant protein PRDX3, thereby reducing ROS‐induced damage. In diabetic foot ulcers, hypoxia, hyperglycemia, and reduced FGF2 and EGF expression lower
Guanglin Niu, Jennifer Geara, Yongjian Chen, Lihua Luo, Yanwei Xiao, Zhuang Liu, Margaux Gaborieau, Ling Pan, Edmund Loh, Dongqing Li, Pehr Sommar, Aoxue Wang, Xiaowei Zheng, Ning Xu Landén   +13 more
wiley   +1 more source

Mitochondrial stress in advanced fibrosis and cirrhosis associated with chronic hepatitis B, chronic hepatitis C, or nonalcoholic steatohepatitis

Hepatology, EarlyView., 2022
Adaptive mitochondrial mechanisms allow mitochondrial resilience and prevent the worsening of fibrosis, while deregulation of these mechanisms promotes the progression from no/minimal‐mild (F0‐F2) fibrosis to advanced fibrosis and cirrhosis (F3‐F4). Abstract Background and Aims Hepatitis B virus (HBV) infection causes oxidative stress (OS) and alters ...
Dimitri Loureiro, Issam Tout, Stéphanie Narguet, Cheikh Mohamed Bed, Morgane Roinard, Ahmad Sleiman, Nathalie Boyer, Nathalie Pons‐Kerjean, Corinne Castelnau, Nathalie Giuly, Dorothy Tonui, Vassili Soumelis, Jamel El Benna, Patrick Soussan, Richard Moreau, Valérie Paradis, Abdellah Mansouri, Tarik Asselah   +17 more
wiley   +1 more source

The Hsp70 co-chaperone Ydj1/HDJ2 regulates ribonucleotide reductase activity.

PLoS Genetics, 2018
Hsp70 is a well-conserved molecular chaperone involved in the folding, stabilization, and eventual degradation of many "client" proteins. Hsp70 is regulated by a suite of co-chaperone molecules that assist in Hsp70-client interaction and stimulate the ...
Isaac T Sluder, Nitika, Laura E Knighton, Andrew W Truman   +3 more
doaj   +1 more source

Cryo‐EM Structures Reveal the Molecular Basis of Asymmetric Allosteric Activation by MMOB in the Hydroxylase of Soluble Methane Monooxygenase

Advanced Science, EarlyView.
Cryo‐EM analysis reveals an asymmetric MMOH–MMOB complex with distinct protomers, where MMOB binding triggers structural rearrangements from the surface to the active site. This conformational asymmetry shortens the Fe···Fe distance to 2.7 Å in one protomer, forming a geometry suitable for O2 activation and supporting a sequential catalytic mechanism ...
Yunha Hwang, Bumhan Ryu, Soyeon Park, Dong‐Heon Lee, Hyo Jin Hong, Jeong‐Geol Na, Chul Gyu Song, Hyun Goo Kang, Edwin Pozharski, Seung Jae Lee   +9 more
wiley   +1 more source

Non‐Targeting shRNA‐Encoded Plasmid DNA Enhances Protective Immunity Through RIDD‐RIG‐I Signaling Pathway in the Zika Virus Animal Model

Advanced Science, EarlyView.
We present a novel DNA vaccine platform featuring intrinsic, non‐targeting dsRNA that significantly enhances immune responses by activating the regulated IRE1‐dependent decay‐RIG‐I signaling pathway. This research elucidates a previously uncharacterized mechanism for dsRNA‐mediated innate immune activation.
Min‐Syuan Huang, Hung‐Chun Liao, Po Peng, Wan‐Ling Wu, Kit Man Chai, Mei‐Yu Chen, Guann‐Yi Yu, Tsung‐Hsien Chuang, Hsin‐Wei Chen, Chuang‐Rung Chang, Shih‐Jen Liu   +10 more
wiley   +1 more source

New Insights into Hsp90 Structural Plasticity Revealed by cryoEM

BioChem
Heat Shock Protein 90 (Hsp90) acts as a crucial molecular chaperone, playing an essential role in activating numerous signaling proteins. The intricate mechanism of Hsp90 involving ATPase-coupled conformational changes and interactions with cochaperone ...
Karine Minari, Vitor Hugo Balasco Serrão, Júlio César Borges   +2 more
doaj   +1 more source