The yeast SNF2/SWI2 protein has DNA-stimulated ATPase activity required for transcriptional activation.

Laurent, Brehon C.; Treich, Isabelle; Carlson, Marian

doi:10.1101/gad.7.4.583

Cited by 285 publications

(224 citation statements)

References 51 publications

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“…This motif was ®rst described following the cloning of the brahma (brm) gene in drosophila (Haynes et al, 1992;Tamkun et al, 1992) and has since been identi®ed in other transcriptional co-activators including the human brahma protein, BRM (Muchardt and Yaniv, 1993) and the yeast protein SNF2/SWI2 (Laurent et al, 1993). The cell cycle gene 1 (CCG1) (Sekiguchi et al, 1991) which was later identi®ed as hTAF II 250 (Hisatake et al, 1993;Ruppert et al, 1993) and shown to be necessary for G1 progression in mammalian cells also contains a bromodomain.…”

Section: Discussionmentioning

confidence: 99%

The cloning, mapping and expression of a novel gene, BRL, related to the AF10 leukaemia gene

McCullagh¹,

Chaplin²,

Meerabux³

et al. 1999

Oncogene

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The MLL gene is reciprocally translocated with one of a number of di erent partner genes in a proportion of human acute leukaemias. The precise mechanism of oncogenic transformation is unclear since most of the partner genes encode unrelated proteins. However, two partner genes, AF10 and AF17 are related through the presence of a cysteine rich region and a leucine zipper. The identi®cation of other proteins with these structures will aid our understanding of their role in normal and leukaemic cells. We report the cloning of a novel human gene (BRL) which encodes a protein containing a cysteine rich region related to that of AF10 and AF17 and is overall most closely related to the previously known protein BR140. BRL maps to chromosome 22q13 and shows high levels of expression in testis and several cell lines. The deduced protein sequence also contains a bromodomain, four potential LXXLL motifs and four predicted nuclear localization signals. A monoclonal antibody raised to a BRL peptide sequence con®rmed its widespread expression as a 120 Kd protein and demonstrated localization to the nucleus within spermatocytes.

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Section: Discussionmentioning

confidence: 99%

The cloning, mapping and expression of a novel gene, BRL, related to the AF10 leukaemia gene

McCullagh¹,

Chaplin²,

Meerabux³

et al. 1999

Oncogene

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“…Other DEAD box proteins could perform functions distinct from RNA unwinding. These possible functions include (1) mediating larger scale RNA structural rearrangements (Figure 10b) (38)(39)(40); (2) altering protein-RNA or protein-protein interactions, analogous to the disruption of protein-DNA contacts in the nucleosome by the Swi/Snf complex ( Figure 10c; the ATPase of the Swi/Snf complex, Swi2/Snf2, is related to the DEAD box family (41,(42)(43)(44)(45)); and (3) functioning, as the G-protein EF-Tu does, as a guarantor of fidelity in RNA-RNA interactions and rearrangements (46). There is no reason to assume a priori that all members of a sequence family of proteins perform the same function.…”

Section: Discussionmentioning

confidence: 99%

The DEAD Box Protein eIF4A. 2. A Cycle of Nucleotide and RNA-Dependent Conformational Changes

1998

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Limited proteolysis experiments have been carried out with the DEAD box protein eIF4A. The results suggest that there is a substantial conformational change in eIF4A upon binding single-stranded RNA. Binding of ADP induces conformational changes in the free enzyme and the enzyme‚RNA complex, and binding of the ATP analogue AMP-PNP induces a conformational change in the enzyme‚RNA complex. The presence or absence of the γ-phosphate on the bound nucleotide acts as a switch, presumably via the Walker motifs, that mediates changes in protein conformation and, as described in the preceding paper in this issue, also mediates changes in RNA affinity. Thus, these results suggest that there is a series of changes in conformation and substrate affinity throughout the ATP hydrolysis reaction cycle. A model is proposed in which eIF4A and the eIF4A-like domains of the DEAD box proteins act as ATPdriven conformational switches or motors that produce movements or structural rearrangements of attached protein domains or associated proteins. These movements could then be used to rearrange RNA structures or RNA‚protein complexes.eIF4A is an RNA-activated ATPase (1, 2) that facilitates binding of the 40S ribosomal subunit to eukaryotic mRNAs (3,4). It is the archetypal member of the DEAD box family of proteins, as the other members of this family are made up of core eIF4A-like domains flanked by N-and C-terminal extensions (5). eIF4A can unwind small duplex RNAs in vitro in conjunction with another factor, eIF4B (2, 6-9). These and other observations have led to the proposal that the DEAD box proteins function as RNA helicases (2,6,8,(10)(11)(12)(13). Nevertheless, few details of the molecular functions or mechanisms of these enzymes are known.In the preceding paper in this issue, a minimal kinetic and thermodynamic framework for the eIF4A-catalyzed ATP hydrolysis reaction was established (14). It was demonstrated that the enzyme's affinity for RNA is modulated by the presence or absence of the γ-phosphate on the bound nucleotide. In addition, UV-induced RNA cross-linking experiments suggested that the presence or absence of the γ-phosphate also alters the conformation of the enzyme (9,14).To further explore ligand-induced conformational changes in eIF4A, limited proteolysis experiments were performed. These experiments provide evidence that distinct conformations of the enzyme are stabilized upon binding of the various combinations of substrates and products. The γ-phosphate of the bound nucleotide plays a key role in inducing both the conformational changes and changes in RNA affinity, suggesting that ATP binding and hydrolysis produce a cycle of conformational and RNA affinity changes in eIF4A. It is proposed that eIF4A and the eIF4A-like domains of the other DEAD box proteins act as ATP-dependent motors that produce motions in attached protein domains or associated proteins. Motions in these domains or associated proteins could then induce structural rearrangements in RNAs or RNA-protein complexes. EXPERIMENTAL PROCE...

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“…In mammals, this complex is composed of more than 10 subunits, and each of the complex contains a single molecule of either Brm or BRG1, but not both (Wang et al, 1996). These two proteins are the catalytic subunits and have DNA-dependent ATPase activity that drives remodeling of nucleosomes (Laurent et al, 1993). We previously reported that Brm and BRG1 have clear differences in their biological activities; Brm is essential for maintenance of murine leukemia virus (MuLV)-based retroviral gene expression, whereas BRG1 is not (Mizutani et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

The Brm gene suppressed at the post-transcriptional level in various human cell lines is inducible by transient HDAC inhibitor treatment, which exhibits antioncogenic potential

et al. 2005

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The mammalian SWI/SNF chromatin remodeling complex is composed of more than 10 protein subunits, and plays important roles in epigenetic regulation. Each complex includes a single BRG1 or Brm molecule as the catalytic subunit. We previously reported that loss of Brm, but not BRG1, causes transcriptional gene silencing of murine leukemia virus-based retrovirus vectors. To understand the biological function and biogenesis of Brm protein, we examined seven cell lines derived from various human tumors that do not produce Brm protein. We show here that these Brm-deficient cell lines transcribe the Brm genes efficiently as detected by nuclear run-on transcription assay, whereas Brm mRNA and Brm hnRNA were undetectable by reverse transcription-polymerase chain reaction analysis. These results indicate that expression of Brm is strongly and promptly suppressed at the posttranscriptional level, through processing and transport of the primary transcript or through stability of mature Brm mRNA. This suppression was attenuated by transient treatment of these cell lines with HDAC inhibitors probably through indirect mechanism. Importantly, all of the treated cells showed prolonged induction of Brm expression after the removal of HDAC inhibitors, and acquired the ability to maintain retroviral gene expression. These results indicate that these Brm-deficient human tumor cell lines carry a functional Brm gene. Treatment with HDAC inhibitors or introduction of exogenous Brm into Brm-deficient cell lines significantly reduced the oncogenic potential as assessed by colonyforming activity in soft agar or invasion into collagen gel, indicating that, like BRG1, Brm is involved in tumor suppression.

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The yeast SNF2/SWI2 protein has DNA-stimulated ATPase activity required for transcriptional activation.

Cited by 285 publications

References 51 publications

The cloning, mapping and expression of a novel gene, BRL, related to the AF10 leukaemia gene

The cloning, mapping and expression of a novel gene, BRL, related to the AF10 leukaemia gene

The DEAD Box Protein eIF4A. 2. A Cycle of Nucleotide and RNA-Dependent Conformational Changes

The Brm gene suppressed at the post-transcriptional level in various human cell lines is inducible by transient HDAC inhibitor treatment, which exhibits antioncogenic potential

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