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Efficacy of glutathione inhibitor eprenetapopt against the vulnerability of glutathione metabolism in SMARCA4-, SMARCB1- and PBRM1-deficient cancer cells.
Sci Rep
December 2024
Division of Cancer Therapeutics, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
Mutation of genes related to the SWI/SNF chromatin remodeling complex is detected in 20% of all cancers. The SWI/SNF chromatin remodeling complex comprises about 15 subunits and is classified into three subcomplexes: cBAF, PBAF, and ncBAF. Previously, we showed that ovarian clear cell carcinoma cells deficient in ARID1A, a subunit of the cBAF complex, are synthetic lethal with several genes required for glutathione (GSH) synthesis and are therefore sensitive to the GSH inhibitor eprenetapopt (APR-246).
View Article and Find Full Text PDFKinetochores get a grip!
J Cell Biol
January 2025
Department of Molecular Genetics I, Faculty of Biology, Center of Medical Biotechnology, University of Duisburg-Essen, Essen, Germany.
A new study by Larson and colleagues (2025. J. Cell Biol.
View Article and Find Full Text PDF[Participation of Proteins of the CPSF Complex in Polyadenylation of Transcripts Read by RNA Polymerase III from SINEs].
Mol Biol (Mosk)
December 2024
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia.
SINEs are mobile genetic elements of multicellular eukaryotes that arose during evolution from various tRNAs, as well as from 5S rRNA and 7SL RNA. Like the genes of these RNAs, SINEs are transcribed by RNA polymerase III. The transcripts of some mammalian SINEs have the capability of AAUAAA-dependent polyadenylation, which is unique for transcript generated by RNA polymerase III.
View Article and Find Full Text PDFPre-ribosomal WDR74 module coordinates the early and late pre-rRNA processing stages for the NVL2-mediated regulation of 60S ribosome biogenesis.
Biochem Biophys Res Commun
January 2025
Laboratory of Molecular and Cellular Biochemistry, Meiji Pharmaceutical University, Kiyose, Tokyo, 204-8588, Japan. Electronic address:
WD repeat domain 74 (WDR74) is a nucleolar protein involved in the early stages of pre-60S maturation in the ribosome biogenesis pathway. In later stages, WDR74 interacts with MTR4, an RNA helicase that functions with the exosome nuclease complex, and is dissociated upon ATP hydrolysis by the chaperone-like nuclear VCP-like 2 (NVL2) AAA-ATPase. We previously reported that ATP hydrolysis-defective NVL2 causes aberrant accumulation of WDR74 on the MTR4-exosome complex at the nucleolar periphery and in the nucleoplasm and that this nuclear redistribution of WDR74 leads to the unusual cleavage of the early rRNA precursor within the internal transcribed spacer 1 sequence.
View Article and Find Full Text PDFA role for the kinetochore protein, NUF2, in ribosome biogenesis.
Mol Biol Cell
December 2024
Dept. of Genetics.
Ribosome biogenesis (RB) is an intricate and evolutionarily conserved process that takes place mainly in the nucleolus and is required for eukaryotic cells to maintain homeostasis, grow in size, and divide. Our laboratory has identified the NUF2 protein, part of the mitotic kinetochore, in a genome-wide siRNA screen for proteins required for making ribosomes in MCF10A human breast epithelial cells (Farley-Barnes, 2018). After rigorous validation and using several biochemical and cell-based assays, we find a role for NUF2 in pre-rRNA transcription, the primary and rate-limiting step of RB.
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