The epidermal growth factor (EGF)-dependent trafficking of the intact EGF receptor to the nucleus and its requirement for growth factor induction of cyclin D and other genes has been reported. Unresolved is the mechanism by which this or other transmembrane proteins are excised from a lipid bilayer before nuclear translocalization. We report that, after the addition of EGF, the cell surface EGF receptor is trafficked to the endoplasmic reticulum (ER) where it associates with Sec61beta, a component of the Sec61 translocon, and is retrotranslocated from the ER to the cytoplasm. Abrogation of Sec61beta expression prevents EGF-dependent localization of EGF receptors to the nucleus and expression of cyclin D. This indicates that EGF receptors are trafficked from the ER to the nucleus by a novel pathway that involves the Sec61 translocon.
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http://dx.doi.org/10.1091/mbc.e06-09-0802 | DOI Listing |
Protein translocation across cellular membranes is an essential and nano-scale dynamic process. In the bacterial cytoplasmic membrane, the core proteins in this process are a membrane protein complex, SecYEG, corresponding to the eukaryotic Sec61 complex, and a cytoplasmic protein, SecA ATPase. Despite more than three decades of extensive research on Sec proteins, from genetic experiments to cutting-edge single-molecule analyses, no study has visually demonstrated protein translocation.
View Article and Find Full Text PDFToxins (Basel)
December 2024
Department of Chemistry, University of Ghana, Legon-Accra P.O. Box LG56, Ghana.
Mycolactone is a complex macrolide toxin produced by , the causative agent of Buruli ulcer. The aim of this paper is to review the chemistry, biosynthetic, and synthetic pathways of mycolactone A/B to help develop an understanding of the mode of action of these polyketides as well as their therapeutic potential. The synthetic work has largely been driven by the desire to afford researchers enough (≥100 mg) of the pure toxins for systematic biological studies toward understanding their very high biological activities.
View Article and Find Full Text PDFSci Rep
November 2024
Department of Biochemistry, College of Allied Sciences, De La Salle Medical and Health Sciences Institute, City of Dasmariñas, Cavite, 4114, Philippines.
Cyclotriazadisulfonamide (CADA) is a macrocyclic compound known for its unique mechanism in inhibiting HIV infection by downregulating the CD4 T-cell receptor, a crucial entry point for the virus. Unlike other antiretrovirals, CADA exhibits activity against a wide range of HIV strains, as all HIV variants require CD4 binding for infection. Furthermore, CADA has shown a synergistic effect with clinically approved anti-HIV drugs, offering potential for enhanced therapeutic strategies (Vermeire & Schols, [65]).
View Article and Find Full Text PDFStructure
January 2025
State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing, China; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China. Electronic address:
Protein translocation systems are essential for distributing proteins across various lipid membranes in cells. Cellular membranes, such as the endoplasmic reticulum (ER) membrane and mitochondrial inner membrane, require highly regulated protein translocation machineries that specifically allow the passage of protein polypeptides while blocking smaller molecules like ions and water. Key translocation systems include the Sec translocation channel, the protein insertases of the Oxa1 superfamily, and the translocases of the mitochondrial inner membrane (TIM).
View Article and Find Full Text PDFCancer Immunol Res
January 2025
Department of Pathology, UMass Chan Medical School, Worcester, Massachusetts.
MHC I antigen presentation allows CD8+ T cells to detect and eliminate cancerous or virally infected cells. The MHC I pathway is not essential for cell growth and viability, so cancers and viruses can evade control by CD8+ T cells by inactivating antigen presentation. In cancers, two common ways for this evasion are the loss of either the MHC I light chain [β2 microglobulin (β2M)] or the transporter-associated with antigen processing (TAP).
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