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A recent in vitro study showed that pharmacological inhibition of the nuclear export receptor XPO1 suppresses oxaliplatin-induced nuclear release of HMGB1 and HMGB2, as well as the translocation of CALR to the plasma membrane. Moreover, cell-targeted-HMGB2 protein potently induced CALR exposure, even in the absence of oxaliplatin.
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http://dx.doi.org/10.1080/2162402X.2024.2421028 | DOI Listing |
ACS Omega
July 2025
The Center of Excellence in Computational Chemistry, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand.
We investigated Mg-mediated inhibition of RyR1 by analyzing solvation, permeation, and binding interactions of Mg, Ca, Na, and K across three functional states: Ca-activated (opRyR1), closed (clRyR1), and Mg-inhibited (HMgRyR1). Using molecular dynamics simulations, potential of mean force (PMF) analysis, quantum mechanical calculations, and MM-GBSA binding free energy calculations, we identified the structural and energetic determinants of Mg inhibition. Our water occupancy analysis reveals that Mg binding at D4945 stabilizes the S6 helical arrangement within the cytoplasmic vestibule in the HMgRyR1 state, maintaining a narrowed pore and reducing water accessibility.
View Article and Find Full Text PDFOncogene
June 2025
Department of Hematology, The Second Affiliated Hospital of Chongqing Medical University, School of Basic Medical Sciences, Chongqing Medical University, Chongqing, China.
Acute myeloid leukemia (AML) represents the most prevalent malignancy within the hematologic system, characterized by refractory relapses and a scarcity of effective treatment options. Karyopherin subunit beta-1 (KPNB1) is a member of karyopherin β family, mediating the nuclear import of its cargoes. In this study, we found that elevated expression levels of KPNB1 are associated with unfavorable outcomes in patients with AML.
View Article and Find Full Text PDFOncoimmunology
December 2024
Centre de Recherche des Cordeliers, Equipe Labellisée par la Ligue Contre le Cancer, Université de Paris Cité, Sorbonne Université, Inserm U1138, Institut Universitaire de France, Paris, France.
A recent in vitro study showed that pharmacological inhibition of the nuclear export receptor XPO1 suppresses oxaliplatin-induced nuclear release of HMGB1 and HMGB2, as well as the translocation of CALR to the plasma membrane. Moreover, cell-targeted-HMGB2 protein potently induced CALR exposure, even in the absence of oxaliplatin.
View Article and Find Full Text PDFCommun Biol
October 2024
Penn/CHOP Center of Excellence in Friedreich's Ataxia, Center of Excellence in Environmental Toxicology, and Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Cisplatin and oxaliplatin cause the secretion of high mobility group box 1 (HMGB1) protein from cancer cells, which is necessary for initiation of immunogenic cell death (ICD). Calreticulin (CRT) translocation from the endoplasmic reticulum to the plasma membrane is also required; oxaliplatin induces this translocation but cisplatin does not. We have discovered that oxaliplatin causes the secretion of both HMGB1 and HMGB2 from the cell nucleus into the extracellular milieu.
View Article and Find Full Text PDFLife Sci
September 2022
Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai, Tamil Nadu 600036, India. Electronic address:
Aims: High mobility group box (HMGB) family proteins, HMGB1, HMGB2, HMGB3, and HMGB4 are oncogenic. The oncogenic nature of HMGB1 is characterized by its association with autophagy, ROS, and MMP. Since HMGB3 is its paralog, we hypothesized that it might also modulate autophagy, ROS, and MMP.
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