L-Ilf3 and L-NF90 Traffic to the Nucleolus Granular Component: Alternatively-Spliced Exon 3 Encodes a Nucleolar Localization Motif

Ilf3 and NF90, two proteins containing double-stranded RNA-binding domains, are generated by alternative splicing and involved in several functions. Their heterogeneity results from posttranscriptional and posttranslational modifications. Alternative splicing of exon 3, coding for a 13 aa N-terminal motif, generates for each protein a long and short isoforms. Subcellular fractionation and localization of recombinant proteins showed that this motif acts as a nucleolar localization signal. Deletion and substitution mutants identified four arginines, essential for nucleolar targeting, and three histidines to stabilize the proteins within the nucleolus. The short isoforms are never found in the nucleoli, whereas the long isoforms are present in the nucleoplasm and the nucleoli. For Ilf3, only the posttranslationally-unmodified long isoform is nucleolar, suggesting that this nucleolar targeting is abrogated by posttranslational modifications. Confocal microscopy and FRAP experiments have shown that the long Ilf3 isoform localizes to the granular component of the nucleolus, and that L-Ilf3 and L-NF90 exchange rapidly between nucleoli. The presence of this 13 aminoacid motif, combined with posttranslational modifications, is responsible for the differences in Ilf3 and NF90 isoforms subcellular localizations. The protein polymorphism of Ilf3/NF90 and the various subcellular localizations of their isoforms may partially explain the various functions previously reported for these proteins

Relations internationales

Durieux Christiane. Relations internationales. In: Diplômées, n°206, 2003. Les Olympes de la parole. p. 174

SUIVI DES INTERACTIONS VIRUS HERPES SIMPLEX TYPE-1 / CELLULES HOTES PAR MICROSCOPIES DE FLUORESCENCE EN CELLULES VIVANTES

LE BUT DE NOTRE TRAVAIL EST DE MIEUX COMPRENDRE LES INTERACTIONS ENTRE CELLULE HOTE DE TYPE NEURONAL ET VIRUS HERPES SIMPLEX TYPE-1 (HSV-1) EN CELLULES VIVANTES. NOS ETUDES ONT ETE EFFECTUEES PAR MICROSCOPIE DE FLUORESCENCE AU NIVEAU UNICELLULAIRE. LA THYMIDINE KINASE (TK) VIRALE A ETE IMPLIQUEE DANS L'ETABLISSEMENT DE LA LATENCE ET LA REACTIVATION. GRACE A DES ETUDES DE DUREES DE VIE DE FLUORESCENCE AU NIVEAU UNICELLULAIRE, NOUS AVONS DETERMINE, PAR DES MESURES DE TRANSFERT D'ENERGIE (FRET ET HOMO-FRET) ENTRE DES VARIANTS SPECTRAUX DE LA GREEN FLUORESCENT PROTEIN (GFP) FUSIONNES AUX EXTREMITES N- OU C-TERMINALES DE LA PROTEINE TK, QUE CELLE-CI EST SOUS FORME DE DIMERES ACTIFS EN CELLULES VIVANTES. DE PLUS, LA DISPARITION DES 10 ACIDES AMINES C-TERMINAUX DE CETTE PROTEINE PROVOQUE UNE DIMINUTION DE 90% DE SON ACTIVITE ENZYMATIQUE. NOUS AVONS CONSTRUIT DEUX VIRUS RECOMBINES EXPRIMANT DES PORTIONS DE TK FUSIONNEES A LA GFP, L'UN DEFICIENT EN TK, L'AUTRE DEFICIENT A LA FOIS EN TK ET EN UL24, ET NOUS LES AVONS CARACTERISES PAR DES TECHNIQUES DE BIOLOGIE MOLECULAIRE ET BIOCHIMIQUES. LE VIRUS DEFICIENT EN UL24 NE MONTRE PAS DE DEFAUT MAJEUR DE REPLICATION EN CELLULES CYCLANTES PAR RAPPORT AUX VIRUS DE PHENOTYPE UL24 SAUVAGE. L'INFECTION DE CELLULES DE TYPE NEURONAL, LES ND7, PAR LE VIRUS KOS SAUVAGE OU PAR L'UN DES DEUX VIRUS RECOMBINES DECLENCHE LES EVENEMENTS PRECOCES DE L'APOPTOSE (DIMINUTION PARTIELLE DU POTENTIEL DE MEMBRANE MITOCHONDRIALE, EXPOSITION DE LA PHOSPHATIDYL SERINE), MAIS N'INDUIT PAS SES EVENEMENTS TARDIFS (CONDENSATION DE LA CHROMATINE, ACTIVATION DES CASPASES). CECI SUGGERE QUE L'APOPTOSE SERAIT BLOQUEE DES LA PREMIERE HEURE APRES L'INFECTION DES CELLULES, PROBABLEMENT PAR L'EXPRESSION D'UNE OU DE PLUSIEURS PROTEINES VIRALES TRES PRECOCES. DE PLUS, NI LA PROTEINE TK, NI LA PROTEINE UL24 NE SEMBLENT IMPLIQUEES DANS L'INDUCTION OU LE BLOCAGE DE L'APOPTOSE INDUITS PAR LES VIRUS. LES PROTEINES VIRALES TARDIVES N'ETANT PAS EXPRIMEES DANS LES ND7, VRAISEMBLABLEMENT AUCUN VIRION MATURE N'EST FORME. CECI SUGGERE QUE CES CELLULES CONSTITUENT UN BON MODELE POUR DES ETUDES DE LA LATENCE DU HSV-1.PARIS-BIUSJ-Thèses (751052125) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Trabectedin-Related Heart Failure: Case Report and a Systematic Review of the Literature

New drugs come not only with benefits but also with unexpected toxicities which need to be promptly recognized and managed. Starting from a scholar case of acute heart failure with preserved ejection fraction following the administration of trabectedin (ET-743, Yondelis®) in a patient with a metastatic solitary fibrous tumor, we performed a systematic review of the literature encompassing the results of previous cardiac safety analysis published ten years ago, a review of clinical trials published during the last 10 years as well as single-case descriptions related to trabectedin cardiotoxicity. The estimated incidence of cardiac toxicity was 3,4% among patients receiving trabectedin, with recent data suggesting a higher rate of heart failure than previously recognized. Previous or concomitant anthracyclines exposure may represent a risk factor. Assaying for NT-pro-BNP may be useful for the early detection of individuals with trabectedin-induced heart failure.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Immunotherapy and targeted therapies efficacy in thymic epithelial tumors : a systematic review

Abstract: Background: Thymic epithelial tumors (TET) are rare neoplasms of the anterior mediastinum. Surgery is the mainstay treatment for resectable TET, whereas systemic treatments are reserved for unresectable and metastatic tumors. The development of new treatments, such as immune checkpoint inhibitors (ICI) and targeted therapies, with promising results in other types of solid tumors, has led to the investigation of their potential efficacy in TET. The study of tumor microenvironments (TME) is another field of investigation that has gained the interest of researchers. Taking into account the complex structure of the thymus and its function in the development of immunity, researchers have focused on TME elements that could predict ICI efficacy. Materials and Methods: The primary objective of this systematic review was to investigate the efficacy of ICI in TET. Secondary objectives included the toxicity of ICI, the efficacy of targeted therapies in TET, and the evaluation of the elements of TME that may be predictive factors of ICI efficacy. A literature search was conducted in February 2023 using the Ovid Medline and SciVerse Scopus databases. Results: 2944 abstracts were retrieved, of which 31 were retained for the systematic review. Five phase II and one retrospective study assessed ICI efficacy. The overall response rate (ORR) varied from 0% to 34%. Median progression-free survival (PFS) ranged from 3.8 to 8.6 months, being lower in thymic carcinoma (TC) (3.8-4.2 months). Median overall survival (OS) ranged from 14.1 to 35.4 months. Treatment-related adverse events occurred in 6.6% to 27.3% of patients. Sixteen studies assessed targeted therapies. The most active molecule was lenvatinib, with 38% ORR in patients with TC while no activity was detected for imatinib, erlotinib plus bevacizumab, and saracatinib. Ten studies assessed TME elements that could predict ICI efficacy. Four studies focused on the tumor-infiltrating immune cells suggesting improved outcomes in patients with TC and high tumor-infiltrating lymphocyte densities. Another study showed that CD8+, CD20+, and CD204+ tumor-infiltrating immune cells in cancer stroma might be prognostic biomarkers in TC. Another study identified the immune-related long non-coding RNAs as a predictor of response to ICI. Tumor mutational burden was identified as a predictive factor of ICI efficacy in one study. Conclusions: Despite study heterogeneity, this review shows that ICI could be a therapeutic option for selected patients with TET that are not amenable to curative radical treatment after first-line chemotherapy

Immunotherapy and Targeted Therapies Efficacy in Thymic Epithelial Tumors: A Systematic Review

info:eu-repo/semantics/publishe

Wavefront engineering microscopy to study 3D mechanotransduction in living cells

We present an experimental system based on the use of a spatial light modulator which enables to perform simultaneously 3D optical manipulation and optical sectioning. This has been achieved by modifying the wave front of the trapping beam with properly diffractive optical elements displayed on a computer controlled spatial light modulator. We demonstrated the capability of the system in two experimental schemes, in a first one we performed a 3D optical scanning of 6 trapped beads by displacing the beads through a fixed imaging plane. In a second one we scan the imaging plane and simultaneously compensate for the movement of the objective in order to keep the trapping plane at a fixed position

Wave front engineering for microscopy of living cells

A new method to perform simultaneously three dimensional optical sectioning and optical manipulation is presented. The system combines a multi trap optical tweezers with a video microscope to enable axial scanning of living cells while maintaining the trapping configuration at a fixed position. This is achieved compensating the axial movement of the objective by shaping the wave front of the trapping beam with properly diffractive optical elements displayed on a computer controlled spatial light modulator. Our method has been validated in three different experimental configurations. In the first, we decouple the position of a trapping plane from the axial movements of the objective and perform optical sectioning of a circle of beads kept on a fixed plane. In a second experiment, we extend the method to living cell microscopy by showing that mechanical constraints can be applied on the dorsal surface of a cell whilst performing its fluorescence optical sectioning. In the third experiment, we trapped beads in a three dimensional geometry and perform, always through the same objective, an axial scan of the volume delimited by the beads