Evidence for a mitochondrial localization of the retinoblastoma protein

<p>Abstract</p> <p>Background</p> <p>The retinoblastoma protein (Rb) plays a central role in the regulation of cell cycle, differentiation and apoptosis. In cancer cells, ablation of Rb function or its pathway is a consequence of genetic inactivation, viral oncoprotein binding or deregulated hyperphosphorylation. Some recent data suggest that Rb relocation could also account for the regulation of its tumor suppressor activity, as is the case for other tumor suppressor proteins, such as p53.</p> <p>Results</p> <p>In this reported study, we present evidence that a fraction of the total amount of Rb protein can localize to the mitochondria in proliferative cells taken from both rodent and human cells. This result is also supported by the use of Rb siRNAs, which substantially reduced the amount of mitochondrial Rb, and by acellular assays, in which [³⁵S]-Methionine-labeled Rb proteins bind strongly to mitochondria isolated from rat liver. Moreover, endogenous Rb is found in an internal compartment of the mitochondria, within the inner-membrane. This is consistent with the protection of Rb from alkaline treatment, which destroys any interaction of proteins that are weakly bound to mitochondria.</p> <p>Conclusion</p> <p>Although a few data regarding an unspecific cytosolic localization of Rb protein have been reported for some tumor cells, our results are the first evidence of a mitochondrial localization of Rb. The mitochondrial localization of Rb is observed in parallel with its classic nuclear location and paves the way for the study of potential as-yet-unknown roles of Rb at this site.</p

L 'apoptose dérive-t-elle de la mort nucléaire programmée mise en œuvre par les protistes ?

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Sentiers de montagne. Réseaux, usages, gestions

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Structural modifications induced by the mtDBP-C protein in the repfication origin of Xenopus laevis mitochondrial DNA

International audienceThe structure of the non-coding region of Xenopus laevis mitochondrial DNA has been studied by electron microscopy analysis of DNA molecules end-labelled with streptavidin-ferritin. We have shown that the effect of a protein modifying the shape of the DNA double-helix can be studied and precisely located by this method. It was found that the non-coding region contains curved segments and that the mitochondrial protein mtDBP-C preferentially enhances the curvature of the promoters-replication origin region. electron microscopy / DNA-binding pro, rein / mitochondrial DNA / DNA bending / DNA curvatur

Une signalisation lysosomale permet un dialogue interorganites améliorant l'activité métabolique, l'homéostasie redox et augmentant la longévité chez Caenorhabditis elegans

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Structural modifications induced by the mtDBP-C protein in the repfication origin of Xenopus laevis mitochondrial DNA

International audienceThe structure of the non-coding region of Xenopus laevis mitochondrial DNA has been studied by electron microscopy analysis of DNA molecules end-labelled with streptavidin-ferritin. We have shown that the effect of a protein modifying the shape of the DNA double-helix can be studied and precisely located by this method. It was found that the non-coding region contains curved segments and that the mitochondrial protein mtDBP-C preferentially enhances the curvature of the promoters-replication origin region

Etude des freins à une installation libérale ou salariée de manière pérenne en soins primaires

PARIS7-Xavier Bichat (751182101) / SudocSudocFranceF

ETUDE DE LA PROTEINE RB DANS L'APOPTOSE INDUITE PAR INACTIVATION DE L'ANTIGENE T DU VIRUS SV40

L'APOPTOSE ET LA SENESCENCE REPLICATIVE SONT DEUX FORMES D'ARRET IRREVERSIBLE DE LA PROLIFERATION CELLULAIRE. L'APOPTOSE EST UNE MORT CELLULAIRE PHYSIOLOGIQUE TANDIS QUE LA SENESCENCE REFLETE LA CAPACITE PROLIFERATIVE LIMITEE DES CELLULES. AFIN D'ETUDIER LE DETERMINISME MOLECULAIRE DE L'ENGAGEMENT DES CELLULES DANS L'APOPTOSE OU LA SENESCENCE, J'AI UTILISE DES FIBROBLASTES DE RAT IMMORTALISES PAR UN MUTANT THERMOSENSIBLE DE L'ANTIGENE T DU VIRUS SV40. A TEMPERATURE RESTRICTIVE, L'ANTIGENE T EST INACTIVE ET LIBERE LA PROTEINE P53 QUI PEUT INDUIRE L'ARRET DE PROLIFERATION ET L'APOPTOSE. LE PHENOTYPE ASSOCIE A LA PERTE DE L'ETAT IMMORTALISE VARIE EN FONCTION DE LA LIGNEE ETUDIEE : LES CELLULES DE LA LIGNEE RETSAF MEURENT PAR APOPTOSE ALORS QUE LES CELLULES DE LA LIGNEE RETSA15 DEVIENNENT SENESCENTES. OUTRE LA PROTEINE P53, L'ANTIGENE T INHIBE LA PROTEINE ONCOSUPPRESSIVE RB. CETTE PROTEINE EST UN REGULATEUR NEGATIF DU FACTEUR DE TRANSCRIPTION E2F-1 QUI FAVORISE L'ENTREE DES CELLULES EN PHASE S DU CYCLE CELLULAIRE AINSI QUE L'EFFET PRO-APOPTOTIQUE DE P53. L'ETUDE COMPARATIVE DES CELLULES RETSAF ET RETSA15 M'A PERMIS D'OBSERVER QUE LA PROTEINE RB EST REGULEE DE FACON DIFFERENTE DANS CES DEUX LIGNEES, A LA FOIS PAR DES PROCESSUS DE PHOSPHORYLATION ET DE CLIVAGE PROTEOLYTIQUE. A TEMPERATURE RESTRICTIVE, L'INACTIVATION DE LA PROTEINE RB PAR PHOSPHORYLATION DANS LES CELLULES RETSAF FAVORISERAIT L'ACTIVITE DU FACTEUR E2F-1, LA PROGRESSION DES CELLULES DANS LE CYCLE CELLULAIRE ET PEUT ETRE L'APOPTOSE. DE FACON SURPRENANTE, LE CLIVAGE DE LA PROTEINE RB PAR DES PROTEASES A CYSTEINE (CASPASES), TELLES QUE LES CASPASES-6 ET -7, FAVORISERAIT LA SURVIE DES CELLULES RETSA15 ET LEUR ARRET DANS LE CYCLE CELLULAIRE. EN ACCORD AVEC CETTE OBSERVATION, J'AI MIS EN EVIDENCE QUE LA PROTEINE BCL-2, UN INHIBITEUR UNIVERSEL DE L'APOPTOSE, FAVORISE LE CLIVAGE DE RB. CETTE PROPRIETE DE BCL-2 POURRAIT PARTICIPER A UNE VOIE D'INHIBITION DE L'APOPTOSE ENCORE JAMAIS DECRITE.PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Studies of specific gene induction during apoptosis of cell lines conditionally immortalized by SV40

International audienceInactivation of SV40 large T antigen, in cells immortalized with conditional mutants, leads to activation of p53 and apoptosis. We have analyzed during this process the expression of genes induced by p53 or differentially expressed during apoptosis in other systems. We find an early induction of Waf1/Cip1. We also observed clusterin is induced late during the process and displays a high level of expression in non-apoptotic cells suggesting a protective role for clusterin. Other genes identified during thymocyte and lymphocyte apoptosis are not induced, showing that the pattern of gene induction is specific to the system studied