Glypican-3 (GPC3) is a cell-surface glycoprotein that is frequently overexpressed in hepatocellular carcinoma (HCC). GPC3 undergoes extensive posttranslational modification (PTM) including cleavage and glycosylation. This review focuses on the structure and function of GPC3 in liver cancer, highlighting the PTM of the tertiary and quaternary structures of GPC3 as a potential oncogenic regulatory mechanism. We propose that the function of GPC3 in normal development can vary with extensive PTM and that dysregulation of these processes leads to disease. Defining the regulatory impact of these modifications can provide a deeper understanding of the role of GPC3 in oncogenesis, epithelial-mesenchymal transition, and drug development. Through review of current literature, this article provides a unique perspective on the role of GPC3 in liver cancer, focusing on potential regulatory mechanisms of PTM on GPC3 function at the molecular, cellular, and disease level.
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http://dx.doi.org/10.1158/0008-5472.CAN-22-3895 | DOI Listing |
Viruses
January 2025
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
The betacoronavirus genus contains five of the seven human coronaviruses, making it a particularly critical area of research to prepare for future viral emergence. We utilized three human betacoronaviruses, one from each subgenus-HCoV-OC43 (embecovirus), SARS-CoV-2 (sarbecovirus), and MERS-CoV (merbecovirus)-, to study betacoronavirus interactions with the PKR-like ER kinase (PERK) pathway of the integrated stress response (ISR)/unfolded protein response (UPR). The PERK pathway becomes activated by an abundance of unfolded proteins within the endoplasmic reticulum (ER), leading to phosphorylation of eIF2α and translational attenuation.
View Article and Find Full Text PDFPathogens
January 2025
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
The papillomavirus E2 protein regulates the transcription, replication, and segregation of viral episomes within the host cell. A multitude of post-translational modifications have been identified which control E2 functions. A highly conserved di-lysine motif within the transactivation domain (TAD) has been shown to regulate the normal functions of the E2 proteins of BPV-1, SfPV1, HPV-16, and HPV-31.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
College of Grassland Science and Technology, Sichuan Agricultural University, Chengdu 611130, China.
As a crucial post-translational modification (PTM), protein ubiquitination mediates the breakdown of particular proteins, which plays a pivotal role in a large number of biological processes including plant growth, development, and stress response. The ubiquitin-proteasome system (UPS) consists of ubiquitin (Ub), ubiquitinase, deubiquitinating enzyme (DUB), and 26S proteasome mediates more than 80% of protein degradation for protein turnover in plants. For the ubiquitinases, including ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), and ubiquitin ligase (E3), the FBK (F-box Kelch repeat protein) is an essential component of multi-subunit E3 ligase SCF (Skp1-Cullin 1-F-box) involved in the specific recognition of target proteins in the UPS.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
School of Pharmacy & Biomolecular Sciences, Faculty of Health, Innovation, Technology and Science, Liverpool John Moores University, James Parsons Building, Byrom Street, Liverpool L3 3AF, UK.
Split inteins are biological mechanisms for the operation of the spatiotemporal control of protein activities. They function through protein -splicing, in which their N- and C-terminal fragments are expressed contiguously with two protein halves. The subsequent self-excision upon recognition of the complimentary fragment yields a mature, complete, and functional protein.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Division of Renal Medicine, Tungs' Taichung MetroHarbor Hospital, Taichung 433, Taiwan.
Oxidative stress, endoplasmic reticulum (ER) stress, and alterations in autophagy activity have been described as prominent factors mediating many pathological processes in chronic kidney disease (CKD). The accumulation of misfolded proteins in the ER may stimulate the unfolded protein response (UPR). The interplay between autophagy and UPR in hemodialysis (HD) patients remains unclear.
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