Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cell cycle arrest is critical for muscle differentiation, and the two processes are closely coordinated but temporally separable. SWI/SNF complexes are ATP-dependent chromatin-remodeling enzymes that have been shown to be required for muscle differentiation in cell culture and have also been reported to be required for Rb-mediated cell cycle arrest. We therefore looked more closely at how SWI/SNF enzymes affect the events that occur during MyoD-induced myogenesis, namely, cell cycle regulation and muscle-specific gene expression, in cells that inducibly express dominant negative versions of Brahma (BRM) and Brahma-related gene 1 (BRG1), the ATPase subunits of two distinct SWI/SNF complexes. Although dominant negative BRM and BRG1 inhibited expression of every muscle-specific regulator and structural gene assayed, there was no effect on MyoD-induced activation of cell cycle regulatory proteins, and thus, cells arrested normally. In particular, in the presence or absence of dominant negative BRM or BRG1, MyoD was able to activate expression of p21, cyclin D3, and Rb, all of which are critical for cell cycle withdrawal in the G1/G0 phase of the cell cycle. These findings suggest that at least one basis for the distinct mechanisms that regulate cessation of cell proliferation and muscle-specific gene expression during muscle differentiation is that SWI/SNF-mediated chromatin-remodeling enzymes are required only for the latter.
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PMID:MyoD can induce cell cycle arrest but not muscle differentiation in the presence of dominant negative SWI/SNF chromatin remodeling enzymes. 1152 99

The members of the Myc/Max/Mad network function as transcriptional regulators. Substantial evidence has been accumulated over the last years that support the model that Myc/Max/Mad proteins affect different aspects of cell behavior, including proliferation, differentiation, and apoptosis, by modulating distinct target genes. The unbalanced expression of these genes, e.g. in response to deregulated Myc expression, is most likely an important aspect of Myc's ability to stimulate tumor formation. Myc and Mad proteins affect target gene expression by recruiting chromatin remodeling activities. In particular Myc interacts with a SWI/SNF-like complex that may contain ATPase activity. In addition Myc binds to TRRAP complexes that possess histone acetyl transferase activity. Mad proteins, that antagonize Myc function, recruit an mSin3 repressor complex with histone deacetylase activity. Thus the antagonism of Myc and Mad proteins is explained at the molecular level by the recruitment of opposing chromatin remodeling activities.
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PMID:Function and regulation of the transcription factors of the Myc/Max/Mad network. 1160 41

ATP-dependent chromatin-remodeling machines of the SWI/SNF family are involved in many cellular processes in eukaryotic nuclei, such as transcription, replication, repair and recombination. Remodeling factors driven by the ATPase ISWI make up a subgroup of this family that exhibits defined mechanistic and functional characteristics. ISWI-induced nucleosome mobility endows nucleosomal arrays with dynamic properties and recent results suggest that ISWI-type remodelers have diverse functions that range from transcriptional regulation to chromatin assembly and maintenance of chromosome structure.
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PMID:Nucleosome mobilization and positioning by ISWI-containing chromatin-remodeling factors. 1168 84

Fanconi anemia (FA) is a genetic disorder that predisposes to hematopoietic failure, birth defects and cancer. We identified an interaction between the FA protein, FANCA and brm-related gene 1 (BRG1) product. BRG1 is a subunit of the SWI/SNF complex, which remodels chromatin structure through a DNA-dependent ATPase activity. FANCA was demonstrated to associate with the endogenous SWI/SNF complex. We also found a significant increase in the molecular chaperone, glucose-regulated protein 94 (GRP94) among BRG1-associated factors isolated from a FANCA-mutant cell line, which was not seen in either a normal control cell line or the mutant line complemented by wild-type FANCA. Despite this specific difference, FANCA did not appear to be absolutely required for in vitro chromatin remodeling. Finally, we demonstrated co-localization in the nucleus between transfected FANCA and BRG1. The physiological action of FANCA on the SWI/SNF complex remains to be clarified, but our work suggests that FANCA may recruit the SWI/SNF complex to target genes, thereby enabling coupled nuclear functions such as transcription and DNA repair.
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PMID:Fanconi anemia protein, FANCA, associates with BRG1, a component of the human SWI/SNF complex. 1172 52

We have dissected the steps in nucleosome remodeling by BRG1, the ATPase subunit of human SWI/SNF. BRG1-catalyzed DNA exposure is not enhanced by the proximity of the site to the ends of nucleosomal DNA, suggesting that the mechanism involves more than peeling or sliding of the DNA. Comparison of DNA exposure at specific sites with overall changes in the path of DNA implies that BRG1 generates multiple distinct remodeled structures and continuously interconverts them. These characteristics are shared by the entire SWI/SNF complex and have parallels, as well as interesting differences, with the activities of GroEL and Hsp70 protein chaperones. The chaperone-like activity of SWI/SNF is expected to create multiple opportunities for the binding of distinct regulatory factors, providing one mechanism by which SWI/SNF family complexes can contribute to both activation and repression of transcription.
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PMID:Generation and interconversion of multiple distinct nucleosomal states as a mechanism for catalyzing chromatin fluidity. 1177 98

Chromatin remodeling is a key step in overcoming the nucleosomal repression of active transcription in eukaryotes. The mammalian SWI/SNF ATP-dependent chromatin-remodeling complexes contain multiple subunits. The ATPase activities in these complexes are attributable to either BRG-1 or the related Brahma protein. The aryl hydrocarbon receptor (AHR), after binding xenobiotic ligands such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), associates with the AHR nuclear translocator (ARNT), and the dimer so formed activates transcription of several genes, including the cytochrome P4501A1 (CYP1A1) gene. We show that BRG-1 potentiates AHR/ARNT-mediated reporter gene activity in a TCDD-dependent fashion in Hepa1c1c7 cells. Introduction of BRG-1 into the BRG-1- and hBrm-deficient SW13 and C33A human cell lines also enhances expression from a transiently transfected AHR/ARNT-dependent reporter gene. Replenishment of BRG-1 to SW13 cells also restores endogenous cytochrome P4501A1 (CYP1A1) gene expression, whereas an ATPase-deficient mutant of BRG-1 is unable to do so. Chromatin immunoprecipitation analysis demonstrated that BRG-1 associates with the enhancer region of the mouse CYP1A1 gene in vivo in a TCDD- and ARNT-dependent fashion, suggesting the specific recruitment of BRG-1 by AHR/ARNT. Finally, we demonstrate that the glutamine-rich subdomain of the transcriptional activation domain of AHR can interact with BRG-1. Together these studies reveal a functional involvement of BRG-1 in activating CYP1A1 gene transcription and implicate the importance of ATP-dependent chromatin remodeling activity on inducible gene expression mediated by AHR/ARNT.
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PMID:Functional involvement of the Brahma/SWI2-related gene 1 protein in cytochrome P4501A1 transcription mediated by the aryl hydrocarbon receptor complex. 1180 98

We show here that murine leukemia virus-based retrovirus vector transgene expression is rapidly silenced in human tumor cell lines lacking expression of Brm, a catalytic subunit of the SWI/SNF chromatin remodeling complex, even though these vectors can successfully enter, integrate, and initiate transcription. We detected this gene silencing as a reduction in the ratio of cells expressing the exogenous gene rather than a reduction in the average expression levels, indicating that down-regulation occurs in an all-or-none manner. Retroviral gene expression was protected from silencing and maintained in Brm-deficient host cells by exogenous expression of Brm but not BRG1, an alternative ATPase subunit in the SWI/SNF complex. Introduction of exogenous Brm to these cells suppressed recruitment of protein complexes containing YY1 and histone deacetylase (HDAC) 1 and 2 to the 5'-long terminal repeat region of the integrated provirus, leading to the enhancement of acetylation of specific lysine residues in histone H4 located in this region. Consistent with these observations, treatment of Brm-deficient cells with HDAC inhibitors but not DNA methylation inhibitors suppressed retroviral gene silencing. These results suggest that the Brm-containing SWI/SNF complex subfamily (trithorax-G) and a complex including YY1 and HDACs (Polycomb-G) counteract each other to maintain transcription of exogenously introduced genes.
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PMID:Maintenance of integrated proviral gene expression requires Brm, a catalytic subunit of SWI/SNF complex. 1185 Apr 27

SWI/SNF regulates growth control, differentiation and tumor suppression, yet few direct targets of this chromatin-remodeling complex have been identified in mammalian cells. We report that SWI/SNF is required for interferon (IFN)-gamma induction of CIITA, the master regulator of major histocompatibility complex class II expression. Despite the presence of functional STAT1, IRF-1 and USF-1, activators implicated in CIITA expression, IFN-gamma did not induce CIITA in cells lacking BRG1 and hBRM, the ATPase subunits of SWI/SNF. Reconstitution with BRG1, but not an ATPase-deficient version of this protein (K798R), rescued CIITA induction, and enhanced the rate of induction of the IFN-gamma-responsive GBP-1 gene. Not ably, BRG1 inhibited the CIITA promoter in transient transfection assays, underscoring the importance of an appropriate chromosomal environment. Chromatin immunoprecipitation revealed that BRG1 interacts directly with the endogenous CIITA promoter in an IFN-gamma-inducible fashion, while in vivo DNase I footprinting and restriction enzyme accessibility assays showed that chromatin remodeling at this locus requires functional BRG1. These data provide the first link between a cytokine pathway and SWI/SNF, and suggest a novel role for this chromatin-remodeling complex in immune surveillance.
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PMID:Interferon-gamma-induced chromatin remodeling at the CIITA locus is BRG1 dependent. 1195 17

An ATP-dependent chromatin remodeling factor, SNF/SWI complex, acts as a coactivator for numerous transcriptional factors. One of the best-documented examples is nuclear receptors, although the molecular mechanism for this coactivation has not been sufficiently elucidated. Here we show that hbrm/hSNF2 alpha and BRG-1/hSNF2 beta, the ATPase subunits of the human SNF/SWI complexes, specifically associate in vitro and in vivo with TATA element modulatory factor (TMF)/ARA160, which has been described as a binding protein to and coactivator for the androgen receptor. This interaction requires highly conserved N-terminal regions of hbrm/hSNF2 alpha and BRG-1/hSNF2 beta and a C-terminal region of TMF/ARA160. Immunofluorescence and Western blot studies revealed that the TMF isoforms differentially localize in the Golgi apparatus and the nucleus.
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PMID:A putative nuclear receptor coactivator (TMF/ARA160) associates with hbrm/hSNF2 alpha and BRG-1/hSNF2 beta and localizes in the Golgi apparatus. 1204 84

The human BRG1 (brahma-related gene 1) protein is a component of the SWI/SNF family of the ATP-dependent chromatin remodelling complexes. We show here that expression of the BRG1 protein, but not of an ATPase-deficient BRG1 protein, in BRG1-deficient SW13 cells alters the organisation of actin filaments. BRG1 expression induces the formation of thick actin filament bundles resembling stress-fibres, structures that are rarely seen in native SW13 cells. BRG1 expression does not influence the activity state of the RhoA-GTPase, which is involved in stress-fibre formation. We find that RhoA is equally activated by stimuli, such as serum, in BRG1-expressing cells, ATPase-deficient BRG1-expressing cells and native SW13 cells. However, the activation of RhoA by lysophosphatidic acid and serum does not trigger the formation of stress-fibre-like structures in SW13 cells. Activation of the RhoA-GTPase in BRG1-expressing cells induces stress-fibre-like structures, indicating that the BRG1 can couple RhoA activation to stress-fibre formation. At least two downstream effectors are involved in stress-fibre formation, Rho-kinase/ROCK and Dia. BRG1 expression, but not the expression of the ATP-deficient BRG1, increases the protein level of ROCK1, one form of the Rho-kinase/ROCK. That this is of importance is supported by the findings that an increased Rho-kinase/ROCK activity in SW13 cells, obtained by overexpressing wild-type ROCK1 and ROCK2, induces stress-fibre formation. No specificity between the two Rho-kinase/ROCK forms exists. Our results suggest that the BRG1 protein affects the RhoA pathway by increasing the protein level of ROCK1, which allows stress-fibre-like structures to form.
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PMID:Expression of BRG1, a human SWI/SNF component, affects the organisation of actin filaments through the RhoA signalling pathway. 1207 64


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