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CRL3 E3 ligase facilitates ubiquitin-mediated degradation of oncogenic SRX to suppress colorectal cancer progression.
Nat Commun
December 2024
School of Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
Article Synopsis
- - The antioxidant protein sulfiredoxin-1 (SRX) is linked to tumor progression in colorectal cancer (CRC) and its degradation mechanism by Keap1, a protein that promotes its breakdown, was studied.
- - Keap1 bound to SRX enhances its degradation via ubiquitination, and its absence leads to increased SRX levels, which accelerates CRC metastasis through the AP-1/MMP9 signaling pathway.
- - Analysis suggests that reduced Keap1 and elevated SRX are associated with worse outcomes in CRC, highlighting the potential of targeting the Keap1-SRX axis for therapeutic strategies.
Dysregulation of protein degradation and alteration of secretome in α-synuclein-exposed astrocytes: implications for dopaminergic neuronal dysfunction.
Cell Commun Signal
December 2024
Department of Biophysics, National Institute of Mental Health and Neurosciences, Institute of National Importance, Bengaluru, Karnataka, 560029, India.
Background: A key factor in the propagation of α-synuclein pathology is the compromised protein quality control system. Variations in membrane association and astrocytic uptake between different α-synuclein forms suggest differences in exocytosis or membrane cleavage, potentially impacting the secretome's influence on dopaminergic neurons. We aimed to understand differences in protein degradation mechanisms of astrocytes for both wild-type (WT) and mutant forms of α-synuclein, specifically during periods of reduced degradation efficiency.
View Article and Find Full Text PDFWithaferin-A induced vimentin S56 phosphorylation dissociates NEDD9 signaling loop to regress progressive metastatic melanoma into lung adenocarcinoma.
Chem Biol Interact
January 2025
Molecular Biomedicine Laboratory, Postgraduate Department of Studies and Research in Biotechnology, Sahyadri Science College, Kuvempu University, Shivamogga, 577203, Karnataka, India. Electronic address:
Article Synopsis
- Metastasis is a complicated disease that relies on specific protein interactions, such as Vimentin and NEDD9, which are crucial for cancer progression and treatment resistance.
- Withaferin A (WFA) is a natural compound thought to target Vimentin, potentially offering a way to inhibit metastasis, although its complete mechanism is still not clear.
- Research has utilized various techniques, including gene expression analysis and protein interaction assays, to demonstrate that targeting the Vimentin-NEDD9 interaction with WFA can reduce melanoma spread to the lungs, highlighting its potential as a therapeutic approach.
Determining key residues of engineered scFv antibody variants with improved MMP-9 binding using deep sequencing and machine learning.
Comput Struct Biotechnol J
December 2024
Department of Chemical and Materials Engineering, University of Nevada, Reno, NV 89557, USA.
Given the crucial role of specific matrix metalloproteinases (MMPs) in the extracellular matrix, an imbalance in the regulation of activation of matrix metalloproteinase-9 (MMP-9) zymogen and inhibition of the enzyme can result in various diseases, such as cancer, neurodegenerative, and gynecological diseases. Thus, developing novel therapeutics that target MMP-9 with single-chain antibody fragments (scFvs) is a promising approach. We used fluorescent-activated cell sorting (FACS) to screen a synthetic scFv antibody library displayed on yeast for enhanced binding to MMP-9.
View Article and Find Full Text PDF[Effect of phosphorylated HSP27 on the proliferation and metastasis of nasopharyngeal carcinoma and its mechanism].
Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
November 2024
Department of Head and Neck Surgery，the Tumor Hospital of Yunnan Province，Kunming，650118，China.
To investigate the effect of phosphorylated HSP27 on the proliferation and metastasis of nasopharyngeal carcinoma and its molecular mechanism. ①Western blot assay was used to detect the expression levels of HSP27 and p-HSP27 in CNE1 and CNE2 cells of nasopharyngeal carcinoma. Inhibited the phosphorylation of HSP27, Transwell assay detected the metastasis ability of nasopharyngeal carcinoma cells.
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