Journal ArticleDOI
Retinoblastoma protein represses transcription by recruiting a histone deacetylase
Laura Magnaghi-Jaulin,R Groisman,Irina Naguibneva,Philippe Robin,S. Lorain,J. P. Le Villain,Frédéric Troalen,Didier Trouche,Annick Harel-Bellan +8 more
TLDR
It is shown here that the histone deacetylase HDAC1 physically interacts and cooperates with Rb, and that the Rb/HDAC1 complex is a key element in the control of cell proliferation and differentiation and that it is a likely target for transforming viruses.Abstract:
The retinoblastoma tumour-suppressor protein Rb inhibits cell proliferation by repressing a subset of genes that are controlled by the E2F family of transcription factors and which are involved in progression from the G1 to the S phase of the cell cycle. Rb, which is recruited to target promoters by E2F1, represses transcription by masking the E2F1 transactivation domain and by inhibiting surrounding enhancer elements, an active repression that could be crucial for the proper control of progression through the cell cycle. Some transcriptional regulators act by acetylating or deacetylating the tails protruding from the core histones, thereby modulating the local structure of chromatin: for example, some transcriptional repressors function through the recruitment of histone deacetylases. We show here that the histone deacetylase HDAC1 physically interacts and cooperates with Rb. In HDAC1, the sequence involved is an LXCXE motif, similar to that used by viral transforming proteins to contact Rb. Our results strongly suggest that the Rb/HDAC1 complex is a key element in the control of cell proliferation and differentiation and that it is a likely target for transforming viruses.read more
Citations
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Journal ArticleDOI
The regulation of E2F by pRB-family proteins
TL;DR: The rapid growth in the size of the E2F literature hides the fact that several fundamental questions have not been fully answered, and the second section of this review details five unresolved issues that have been highlighted by recent publications.
Journal ArticleDOI
The history of cancer epigenetics.
TL;DR: This timeline traces the field from its conception to the present day and addresses the genetic basis of epigenetic changes — an emerging area that promises to unite cancer genetics and epigenetics, and might serve as a model for understanding the epigenetic basis of human disease more generally.
Journal ArticleDOI
Transcription regulation by histone methylation: interplay between different covalent modifications of the core histone tails
Yi Zhang,Danny Reinberg +1 more
TL;DR: This work aims to demonstrate the efforts towards in-situ applicability of EMMARM, which aims to provide real-time information about the “building blocks” of EMT and its role in cancer progression.
Journal ArticleDOI
Truncating Mutations of hSNF5/INI1 in Aggressive Paediatric Cancer
Isabella Versteege,Nicolas Sevenet,Julian Lange,Marie-Françoise Rousseau-Merck,Peter F. Ambros,Rupert Handgretinger,Alain Aurias,Olivier Delattre +7 more
TL;DR: The observation of bi-allelic alterations of hSNF5/INI1 in MRTs suggests that loss-of-function mutations of h snf5/inI1 contribute to oncogenesis, and the most frequently deleted part of chromosome 22q11.2 is mapped.
Journal Article
The Pezcoller lecture: cancer cell cycles revisited.
TL;DR: Lesions in the p16--cyclin D-CDK4--Rb and ARF--Mdm2--p53 pathways occur so frequently in cancer, regardless of patient age or tumor type, that they appear to be part of the life history of most, if not all, cancer cells.
References
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Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei
TL;DR: A procedure for preparing extracts from nuclei of human tissue culture cells that directs accurate transcription initiation in vitro from class II promoters, including tRNA and Ad 2 VA, is developed.
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The Transcriptional Coactivators p300 and CBP Are Histone Acetyltransferases
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Activation of p53 Sequence-Specific DNA Binding by Acetylation of the p53 C-Terminal Domain
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TL;DR: It is demonstrated that p53 can be modified by acetylated both in vivo and in vitro, indicating a novel pathway for p53 activation and providing an example of an acetylation-mediated change in the function of a nonhistone regulatory protein.
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TL;DR: Results clearly indicate that TSA is a potent and specific inhibitor of the histone deacetylase and that the in vivo effect of TSA on cell proliferation and differentiation can be attributed to the inhibition of the enzyme.
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A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3p.
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