In the originally published version of this Article, the authors Sai-Juan Chen and Zhu Chen were incorrectly listed as being affiliated with 'University Paris Diderot, Sorbonne Paris Cité, INSERM U944, CNRS UMR7212, Equipe labellisée LNCC, Hôpital St. Louis 1, Paris 75475, France', and the affiliation 'Institute of Health Sciences, Shanghai Institutes for Biological Sciences and Graduate School, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China' was inadvertently omitted. These errors have now been corrected in both the PDF and HTML versions of the Article.
View Article and Find Full Text PDFProMyelocyticLeukemia nuclear bodies (PML NBs) are stress-regulated domains directly implicated in acute promyelocytic leukemia eradication. Most TRIM family members bind ubiquitin E2s and many acquire ligase activity upon RING dimerization. In contrast, PML binds UBC9, the SUMO E2 enzyme.
View Article and Find Full Text PDFIntroduction: Targeted therapies such as tyrosine kinase inhibitors (TKIs) have dramatically improved the treatment of lung adenocarcinoma, and detection of activating mutations of genes such as EGFR or anaplastic lymphoma kinase gene (ALK) is now mandatory in the clinical setting. However, additional targetable alterations are continuously being described and forcing us to adapt our detection methods. Here we have evaluated the ability of eight amplicon-based next-generation sequencing (NGS) panels to detect the recently described mesenchymal epithelial transition factor (MET) exon 14 (METex14) alterations or new mutations conferring resistance to TKIs.
View Article and Find Full Text PDFHepatitis B virus infection (HBV) is a major risk factor for the development of hepatocellular carcinoma. HBV replicates from a covalently closed circular DNA (cccDNA) that remains as an episome within the nucleus of infected cells and serves as a template for the transcription of HBV RNAs. The regulatory protein HBx has been shown to be essential for cccDNA transcription in the context of infection.
View Article and Find Full Text PDFThe promyelocytic leukemia (PML) protein organizes PML nuclear bodies (NBs), which are stress-responsive domains where many partner proteins accumulate. Here, we clarify the basis for NB formation and identify stress-induced partner sumoylation as the primary NB function. NB nucleation does not rely primarily on intermolecular interactions between the PML SUMO-interacting motif (SIM) and SUMO, but instead results from oxidation-mediated PML multimerization.
View Article and Find Full Text PDFThe hepatitis B virus X protein (HBx) is essential for virus replication and has been implicated in the development of liver cancer. HBx is recruited to viral and cellular promoters and activates transcription by interacting with transcription factors and coactivators. Here, we purified HBx-associated factors in nuclear extracts from HepG2 hepatoma cells and identified protein arginine methyltransferase 1 (PRMT1) as a novel HBx-interacting protein.
View Article and Find Full Text PDFThe regulatory protein HBx is essential for hepatitis B virus (HBV) replication in vivo and for transcription of the episomal HBV genome. We previously reported that in infected cells HBx activates genes targeted by the transcription factor CREB [cyclic adenosine monophosphate (cAMP) response element-binding protein]. cAMP induces phosphorylation and activation of CREB, and CREB inactivation is promoted by protein phosphatase 1 (PP1), which binds to CREB through histone deacetylase 1 (HDAC1).
View Article and Find Full Text PDFEpidemiological studies have provided overwhelming evidence for a causal role of chronic HBV infection in the development of hepatocellular carcinoma (HCC), but the molecular mechanisms underlying virally-induced tumorigenesis remain largely debated. In the absence of a dominant oncogene encoded by the HBV genome, indirect roles have been proposed, including insertional activation of cellular oncogenes by HBV DNA integration, induction of genetic instability by viral integration or by the regulatory protein HBx, and long term effects of viral proteins in enhancing immune-mediated liver disease. In this chapter, we discuss different models of HBV-mediated liver cell transformation based on animal systems of hepadnavirus infection as well as functional studies in hepatocyte and hepatoma cell lines.
View Article and Find Full Text PDFDespite the existence of effective vaccines, HBV infection remains a major health problem with 2 billion people infected worldwide. Among them, 350 million are chronically infected, a major risk factor for the development of hepatocellular carcinoma (HCC). There is a strong need to develop new and efficient treatments against chronic infection and HCC.
View Article and Find Full Text PDFIn acute promyelocytic leukaemia (APL), arsenic trioxide induces degradation of the fusion protein encoded by the PML-RARA oncogene, differentiation of leukaemic cells and produces clinical remissions. SUMOylation of its PML moiety was previously implicated, but the nature of the degradation pathway involved and the role of PML-RARalpha catabolism in the response to therapy have both remained elusive. Here, we demonstrate that arsenic-induced PML SUMOylation triggers its Lys 48-linked polyubiquitination and proteasome-dependent degradation.
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