The nuclear export protein chromosomal region maintenance/exportin 1/Xpo1 (CRM1) is involved in the nuclear export of proteins and messenger RNAs and, thus, mediates the subcellular distribution of important molecules. Osteosarcoma is a ubiquitous and highly aggressive malignant bone tumor. The expression of CRM1 protein in human osteosarcoma has not been reported to date. We investigated the expression of CRM1 in 57 human osteosarcoma and 5 normal cartilage tissues. Western blot investigation revealed expression of CRM1 was significantly increased in osteosarcoma compared with normal tissues. High expression of CRM1 was significantly associated with increased serum level of alkaline phosphatase (ALP, P=0.001) but did not associate with that of lactate dehydrogenase (LDH, P=0.06). In univariate analysis, a significant association between CRM1 expression and tumor size (P=0.014) as well as histological grade (P=0.003) was observed, while high CRM1 expression was not correlated with the other clinicopathological parameters. In Kaplan-Meier survival analysis, high CRM1 expression was a significant prognostic indicator for progression-free survival (P=0.016) as well as overall survival (P=0.008). Multivariate analysis demonstrated that expression of CRM1 was an independent prognostic parameter for longer overall survival (95% CI, 1.27-5.39). Additional prospective studies are required to investigate the prognostic role of high expression of CRM1.
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bioRxiv
December 2024
Department of Structural Biology, Van Andel Institute, Grand Rapids, MI, USA.
Histone H3K9 methylation (H3K9me) by Setdb1 silences retrotransposons (rTE) by sequestering them in constitutive heterochromatin. Atf7IP is a constitutive binding partner of Setdb1 and is responsible for Setdb1 nuclear localization, activation and chromatin recruitment. However, structural details of the Setdb1/Atf7IP interaction have not been evaluated.
View Article and Find Full Text PDFMethods Mol Biol
November 2024
Department of Cancer Biology, Sols-Morreale Biomedical Research Institute (IIBM), Spanish National Research Council (CSIC), Universidad Autónoma de Madrid (UAM), Madrid, Spain.
FOXO3 is a transcription factor that mainly exerts its functions in the cell nucleus. The amino acid sequence of FOXO3 contains a nuclear localization sequence (NLS) and a nuclear export sequence (NES) allowing for nuclear/cytoplasmic shuttling that plays an important role in regulating FOXO3 activity. Nuclear accumulation of FOXO3 proteins can be the result of translocation to the nucleus triggered by upstream regulatory input or trapping of FOXO3 within the nucleus through the inhibition of its nuclear export via the receptor CRM1.
View Article and Find Full Text PDFVet Microbiol
November 2024
National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China. Electronic address:
Coronaviruses are causing epizootic diseases and thus are a substantial threat for both domestic and wild animals. These viruses depend on the host translation machinery to complete their life cycle. The current paper identified cellular RNA-binding proteins (RBPs), La-related protein 4 (LARP4) and polyadenylate-binding protein cytoplasmic 1 (PABPC1), as critical regulators of efficient translation of the coronavirus porcine epidemic diarrhea virus (PEDV) mRNA.
View Article and Find Full Text PDFSci Adv
August 2024
School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
XPO1 (Exportin-1/CRM1) is a nuclear export protein that is frequently overexpressed in cancer and functions as a driver of oncogenesis. Currently small molecules that target XPO1 are being used in the clinic as anticancer agents. We identify XPO1 as a target for natural killer (NK) cells.
View Article and Find Full Text PDFJ Adv Res
July 2024
College of Veterinary Medicine, Shandong Provincial Key Laboratory of Zoonoses, Shandong Agricultural University, 7 Panhe Street, Tai'an City, 271017, Shandong Province, China. Electronic address:
Introduction: Environmental and occupational exposure to cadmium (Cd) has been shown to cause acute kidney injury (AKI). Previous studies have demonstrated that autophagy inhibition and lysosomal dysfunction are important mechanisms of Cd-induced AKI.
Objectives: Transcription factor EB (TFEB) is a critical transcription regulator that modulates autophagy-lysosome function, but its role in Cd-induced AKI is yet to be elucidated.
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