The mammalian SWI/SNF complex and the control of cell growth.
The mammalian SWI/SNF complex is a chromatin remodelling complex that uses the energy of ATP hydrolysis to facilitate access of transcription factors to regulatory DNA sequences. This complex, that was initially described as a co-factor for nuclear receptors, has recently been associated with the control of cell growth. Two of the subunits known as BRG-1 and brm can associate with the Retinoblastoma tumour suppressor gene product and co-operate with this protein for repression of E2F activity. In addition, expression of brm is frequently down-regulated upon cellular transformation and re-introduction of this protein into fibroblasts transformed by activated ras induces partial reversion of the transformed phenotype. Finally, the hSNF5/INI1 gene, encoding another subunit of the SWI/SNF complex, is subject to bi-allelic mutations in rhabdoid tumours, a very aggressive form of paediatric cancers. These observations provide a novel link between malignant transformation and chromatin remodelling machineries.
Muchardt
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Unite@a3 des Virus Oncoge@a4nes, URA1644 du CNRS, De@a3partement des Biotechnologies, Institut Pasteur, 25 rue du Docteur Roux, Paris, Cedex 15, 75724, France.
Yaniv
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D016475:3T3 Cells; D000251:Adenosine Triphosphatases; D000818:Animals; D002352:Carrier Proteins; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000235:genetics / Q000502:physiology; D002472:Cell Transformation, Viral; D002843:Chromatin / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D029721:Drosophila Proteins; D050684:E2F Transcription Factors; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D011905:Genes, ras; D006367:HeLa Cells; D006801:Humans; D019476:Insect Proteins / Q000235:genetics / Q000502:physiology; D051379:Mice; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000502:physiology; D009687:Nuclear Proteins / Q000502:physiology*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D016601:RNA-Binding Proteins; D016160:Retinoblastoma Protein / Q000502:physiology; D056465:Retinoblastoma-Binding Protein 1; D018335:Rhabdoid Tumor / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000235:genetics / Q000502:physiology; D000071796:SMARCB1 Protein; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
C533431:Arid4a protein, mouse; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C088053:Dp transcription factor, Drosophila; D029721:Drosophila Proteins; D050684:E2F Transcription Factors; D005656:Fungal Proteins; D019476:Insect Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D016160:Retinoblastoma Protein; D056465:Retinoblastoma-Binding Protein 1; D017412:Ribonucleoprotein, U1 Small Nuclear; C499336:SMARCA1 protein, human; C084011:SMARCA2 protein, human; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; C066190:SNF5 protein, S cerevisiae; C078562:SWI1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C499503:Smarca2 protein, mouse; C513265:Smarcb1 protein, mouse; D015534:Trans-Activators; D050680:Transcription Factor DP1; D014157:Transcription Factors; C089969:snf protein, Drosophila; D000251:Adenosine Triphosphatases; C084108:SMARCA4 protein, human; C499333:SNF2 protein, S cerevisiae; C513194:Smarca4 protein, mouse; D004265:DNA Helicases