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

---

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

Mammalian SWI/SNF-related chromatin remodeling complexes are required for transcription controls that underlie differentiation, development, and tumor suppression. The complexes each consist of an ATPase of the SWI2/SNF2 family and approximately seven stably associated non-catalytic subunits. In spite of the importance of these complexes to biological processes, monoclonal antibodies to the various subunits have not been readily available. Mammalian complexes can vary in subunit composition, but the BAF155 (SMARCC1) subunit and a closely related protein, BAF170 (SMARCC2), appear to be ubiquitous components. Here we report the development of antibodies raised against a BAF155-derived peptide. The antibodies were raised against a single peptide of 18 amino acids. However, hybridomas expressing antibodies of two different specificities were isolated. One, designated DXD7, is specific for BAF155. The other, designated DXD12, is reactive with both BAF155 and BAF170. The antibodies are reactive against both native and denatured proteins, and are suitable for immunoprecipitation and Western blots. The DXD7 antibody is suitable additionally for immunofluorescence assays.
...
PMID:Monoclonal antibodies reactive with the BAF155 (SMARCC1) and BAF170 (SMARCC2) components of human SWI/SNF-related complexes. 1578 10

SWITCH/SUCROSE NONFERMENTING (SWI/SNF) chromatin-remodeling complexes mediate ATP-dependent alterations of DNA-histone contacts. The minimal functional core of conserved SWI/SNF complexes consists of a SWI2/SNF2 ATPase, SNF5, SWP73, and a pair of SWI3 subunits. Because of early duplication of the SWI3 gene family in plants, Arabidopsis thaliana encodes four SWI3-like proteins that show remarkable functional diversification. Whereas ATSWI3A and ATSWI3B form homodimers and heterodimers and interact with BSH/SNF5, ATSWI3C, and the flowering regulator FCA, ATSWI3D can only bind ATSWI3B in yeast two-hybrid assays. Mutations of ATSWI3A and ATSWI3B arrest embryo development at the globular stage. By a possible imprinting effect, the atswi3b mutations result in death for approximately half of both macrospores and microspores. Mutations in ATSWI3C cause semidwarf stature, inhibition of root elongation, leaf curling, aberrant stamen development, and reduced fertility. Plants carrying atswi3d mutations display severe dwarfism, alterations in the number and development of flower organs, and complete male and female sterility. These data indicate that, by possible contribution to the combinatorial assembly of different SWI/SNF complexes, the ATSWI3 proteins perform nonredundant regulatory functions that affect embryogenesis and both the vegetative and reproductive phases of plant development.
...
PMID:SWI3 subunits of putative SWI/SNF chromatin-remodeling complexes play distinct roles during Arabidopsis development. 1605 36

Eaf1 (for Esa1-associated factor 1) and Eaf2 have been identified as stable subunits of NuA4, a yeast histone H4/H2A acetyltransferase complex implicated in gene regulation and DNA repair. While both SWI3-ADA2-N-CoR-TF IIIB domain-containing proteins are required for normal cell cycle progression, their depletion does not affect the global Esa1-dependent acetylation of histones. In contrast to all other subunits, Eaf1 is found exclusively associated with the NuA4 complex in vivo. It serves as a platform that coordinates the assembly of functional groups of subunits into the native NuA4 complex. Eaf1 shows structural similarities with human p400/Domino, a subunit of the NuA4-related TIP60 complex. On the other hand, p400 also possesses an SWI2/SNF2 family ATPase domain that is absent from the yeast NuA4 complex. This domain is highly related to the yeast Swr1 protein, which is responsible for the incorporation of histone variant H2AZ in chromatin. Since all of the components of the TIP60 complex are homologous to SWR1 or NuA4 subunits, we proposed that the human complex corresponds to a physical merge of two yeast complexes. p400 function in TIP60 then would be accomplished in yeast by cooperation between SWR1 and NuA4. In agreement with such a model, NuA4 and SWR1 mutants show strong genetic interactions, NuA4 affects histone H2AZ incorporation/acetylation in vivo, and both preset the PHO5 promoter for activation. Interestingly, the expression of a chimeric Eaf1-Swr1 protein recreates a single human-like complex in yeast cells. Our results identified the key central subunit for the structure and functions of the NuA4 histone acetyltransferase complex and functionally linked this activity with the histone variant H2AZ from yeast to human cells.
...
PMID:Eaf1 is the platform for NuA4 molecular assembly that evolutionarily links chromatin acetylation to ATP-dependent exchange of histone H2A variants. 1821 47

In yeast and mammals, ATP-dependent chromatin remodelling complexes of the SWI/SNF family play critical roles in the regulation of transcription, cell proliferation, differentiation and development. Homologues of conserved subunits of SWI/SNF-type complexes, including Snf2-type ATPases and SWI3-type proteins, participate in analogous processes in Arabidopsis. Recent studies indicate a remarkable similarity between phenotypic effects of mutations in the SWI3 homologue ATSWI3C and bromodomain-ATPase BRM genes. To verify the extent of functional similarity between BRM and ATSWI3C, we have constructed atswi3c brm double mutants and compared their phenotypic traits to those of simultaneously grown single atswi3c and brm mutants. In addition to inheritance of characteristic developmental abnormalities shared by atswi3c and brm mutants, some additive brm-specific traits were also observed in the atswi3c brm double mutants. Unlike atswi3c, the brm mutation results in the enhancement of abnormal carpel development and pollen abortion leading to complete male sterility. Despite the overall similarity of brm and atswi3c phenotypes, a critical requirement for BRM in the differentiation of reproductive organs suggests that its regulatory functions do not entirely overlap those of ATSWI3C. The detection of two different transcript isoforms indicates that BRM is regulated by alternative splicing that creates an in-frame premature translation stop codon in its SNF2-like ATPase coding domain. The analysis of Arabidopsis mutants in nonsense-mediated decay suggests an involvement of this pathway in the control of alternative BRM transcript level.
...
PMID:Genetic analysis of functional redundancy of BRM ATPase and ATSWI3C subunits of Arabidopsis SWI/SNF chromatin remodelling complexes. 1930 Oct 30

The TIP60 histone acetyltransferase plays diverse roles in DNA damage responses, DNA double-strand break repair, and transcriptional regulation. TIP60 resides within a multisubunit complex that has been shown to be targeted by transcription factors and to be involved in histone acetylation and transcriptional activation. p400, an SWI2/SNF2-related ATPase that serves as an ATP-dependent chromatin remodeling enzyme, exists as an integral subunit of a TIP60 complex but also resides within a distinct complex that presumably lacks TIP60 and appears to be involved in the transcriptional repression of basal p53 target gene expression. Here, we describe a TIP60-containing p400 complex population in which the acetyltransferase activity of TIP60 is repressed by interactions with p400. We further show that an SWI3-ADA2-N-CoR-TFIIIB (SANT) domain of p400 binds directly to the histone acetyltransferase (HAT) domain of TIP60 and blocks both its enzymatic activity and its coactivator function in regulating basal p21 gene expression. Our results thus suggest that p400 represses basal p21 gene expression through dual mechanisms that include the direct inhibition of TIP60 enzymatic activity described here and the previously described ATP-dependent positioning of H2A.Z at the promoter.
...
PMID:The SANT domain of p400 ATPase represses acetyltransferase activity and coactivator function of TIP60 in basal p21 gene expression. 2035 Nov 80

The mammalian SWI/SNF chromatin remodeling complex is a key player in multiple chromatin transactions. Core subunits of this complex, including the ATPase, Brg-1, and various Brg-1-associated factors (BAFs), work in concert to maintain a functional remodeling complex. This intra-complex regulation is supervised by protein-protein interactions, as stoichiometric levels of BAF proteins are maintained by proteasomal degradation. We show that the mechanism of BAF155-mediated stabilization of BAF57 involves blocking its ubiquitination by preventing interaction with TRIP12, an E3 ubiquitin ligase. Consequently, as opposed to complexed BAF57, whose principal lysines are unavailable for ubiquitination, uncomplexed BAF57 can be freely ubiquitinated and degraded by the proteasome. Additionally, a BAF57 mutant, which contains no lysine residues, was found to retain its ability to be stabilized by interaction with BAF155, suggesting that in addition to the ubiquitin-dependent mechanism of BAF57 degradation, there exists a ubiquitin-independent mechanism that may involve the direct interaction of BAF57 with the proteasome. We propose that this regulatory mechanism exists to ensure functional fidelity of the complex and prevent the accumulation of uncomplexed proteins, which may disrupt the normal activity of the complex.
...
PMID:Ubiquitin-dependent and ubiquitin-independent control of subunit stoichiometry in the SWI/SNF complex. 2082 58

The E2F6 protein functions as an Rb-independent repressor of gene transcription. We have previously provided evidence suggesting a role for E2F6 in repression of E2F-responsive genes at S phase. Here, we have identified BRG1, the ATPase subunit of the SWI/SNF chromatin-remodeling complex, as an E2F6 interacting protein. Immunoprecipitation experiments demonstrate that BRG1 binds specifically to E2F6 and E2F4 but not the activator E2Fs. E2F6 was also able to interact with BAF155, a BRG1-associated factor, in the SWI/SNF complex. Chromatin immunoprecipitation assays demonstrate the binding of BRG1 coincident with E2F6 on G1/S gene promoters during S phase. Collectively, our studies suggest that E2F6 may recruit BRG1 in transcriptional regulation of genes important for G1/S phase transition of the cell cycle.
...
PMID:E2F6 associates with BRG1 in transcriptional regulation. 2308 33

The SWI/SNF chromatin-remodeling family contains various protein complexes, which regulate gene expression during cellular development and influence DNA damage response in an ATP- and complex-dependent manner, of which details remain elusive. Recent human genome sequencing of various cancer cells revealed frequent mutations in SWI/SNF factors, especially ARID1A, a variant subunit in the BRG1-associated factor (BAF) complex of the SWI/SNF family. We combined live-cell analysis and gene-suppression experiments to show that suppression of either ARID1A or its paralog ARID1B led to reduced nonhomologous end joining activity of DNA double-strand breaks (DSB), decreased accumulation of KU70/KU80 proteins at DSB, and sensitivity to ionizing radiation, as well as to cisplatin and UV. Thus, in contrast to transcriptional regulation, both ARID1 proteins are required for cellular resistance to various types of DNA damage, including DSB. The suppression of other SWI/SNF factors, namely SNF5, BAF60a, BAF60c, BAF155, or BAF170, exhibits a similar phenotype. Of these factors, ARID1A, ARID1B, SNF5, and BAF60c are necessary for the immediate recruitment of the ATPase subunit of the SWI/SNF complex to DSB, arguing that both ARID1 proteins facilitate the damage response of the complex. Finally, we found interdependent protein stability among the SWI/SNF factors, suggesting their direct interaction within the complex and the reason why multiple factors are frequently lost in parallel in cancer cells. Taken together, we show that cancer cells lacking in the expression of certain SWI/SNF factors, including ARID1A, are deficient in DNA repair and potentially vulnerable to DNA damage.
...
PMID:SWI/SNF factors required for cellular resistance to DNA damage include ARID1A and ARID1B and show interdependent protein stability. 2478 99

The mammalian SWI/SNF chromatin remodeling complex is a heterogeneous collection of related protein complexes required for gene regulation and genome integrity. It contains a central ATPase (BRM or BRG1) and various combinations of 10-14 accessory subunits (BAFs for BRM/BRG1 Associated Factors). Two distinct complexes differing in size, BAF and the slightly larger polybromo-BAF (PBAF), share many of the same core subunits but are differentiated primarily by having either AT-rich interaction domain 1A/B (ARID1A/B in BAF) or ARID2 (in PBAF). Using density gradient centrifugation and immunoprecipitation, we have identified and characterized a third and smaller SWI/SNF subcomplex. We termed this complex GBAF because it incorporates two mutually exclusive paralogs, GLTSCR1 (glioma tumor suppressor candidate region gene 1) or GLTSCR1L (GLTSCR1-like), instead of an ARID protein. In addition to GLTSCR1 or GLTSCR1L, the GBAF complex contains BRD9 (bromodomain-containing 9) and the BAF subunits BAF155, BAF60, SS18, BAF53a, and BRG1/BRM. We observed that GBAF does not contain the core BAF subunits BAF45, BAF47, or BAF57. Even without these subunits, GBAF displayed in vitro ATPase activity and bulk chromatin affinity comparable to those of BAF. GBAF associated with BRD4, but, unlike BRD4, the GBAF component GLTSCR1 was not required for the viability of the LNCaP prostate cancer cell line. In contrast, GLTSCR1 or GLTSCR1L knockouts in the metastatic prostate cancer cell line PC3 resulted in a loss in proliferation and colony-forming ability. Taken together, our results provide evidence for a compositionally novel SWI/SNF subcomplex with cell type-specific functions.
...
PMID:Glioma tumor suppressor candidate region gene 1 (GLTSCR1) and its paralog GLTSCR1-like form SWI/SNF chromatin remodeling subcomplexes. 2937 58

Epigenetic enzymes regulate higher-order chromatin architecture and cell-type specific gene expression. The ATPase BRG1 and the SWI/SNF chromatin remodeling complex are epigenetic enzymes that regulate chromatin accessibility during steady and transitional cell states. Experiments in mice show that the loss of BRG1 inhibits cellular reprogramming, while studies using human cells demonstrate that the overexpression of BRG1 enhances reprogramming. We hypothesized that the variation of SWI/SNF subunit expression in the human population would contribute to variability in the efficiency of induced pluripotent stem cells (iPSC) reprogramming. To examine the impact of an individual's sex, ancestry, and age on iPSC reprogramming, we created a novel sex and ancestry balanced cohort of 240 iPSC lines derived from human dermal fibroblasts (DF) from 80 heathy donors. We methodically assessed the reprogramming efficiency of each DF line and then quantified the individual and demographic-specific variations in SWI/SNF chromatin remodeling proteins and mRNA expression. We identified BRG1, BAF155, and BAF60a expression as strongly correlating with iPSC reprogramming efficiency. Additionally, we discovered that high efficiency iPSC reprograming is negatively correlated with donor age, positively correlated with African American descent, and uncorrelated with donor sex. These results show the variations in chromatin remodeling protein expression have a strong impact on iPSC reprogramming. Additionally, our cohort is unique in its large size, diversity, and focus on healthy donors. Consequently, this cohort can be a vital tool for researchers seeking to validate observational results from human population studies and perform detailed mechanistic studies in a controlled cell culture environment. Stem Cells 2018;36:1697-1708.
...
PMID:Epigenetic Enzymes, Age, and Ancestry Regulate the Efficiency of Human iPSC Reprogramming. 3015 70


<< Previous 1 2 3 Next >>

---