scholarly journals Structure of the BRK domain of the SWI/SNF chromatin remodeling complex subunit BRG1 reveals a potential role in protein–protein interactions

2020 ◽  
Vol 29 (4) ◽  
pp. 1033-1039 ◽  
Author(s):  
Mark D. Allen ◽  
Mark Bycroft ◽  
Giovanna Zinzalla
Keyword(s):  
Chromatin Remodeling ◽  
Protein Interactions ◽  
Potential Role ◽  
Protein Protein Interactions ◽  
Chromatin Remodeling Complex

scholarly journals Regulating SWI/SNF Subunit Levels via Protein-Protein Interactions and Proteasomal Degradation: BAF155 and BAF170 Limit Expression of BAF57

2005 ◽  
Vol 25 (20) ◽  
pp. 9016-9027 ◽  
Author(s):  
Jianguang Chen ◽  
Trevor K. Archer
Keyword(s):  
Chromatin Remodeling ◽  
Protein Interactions ◽  
Wild Type ◽  
Protein Protein Interactions ◽  
Physiological Mechanisms ◽  
Protein Levels ◽  
Chromatin Remodeling Complex ◽  
Exogenous Expression ◽  
Protein Components ◽  
Enzyme Complexes

ABSTRACT The mammalian SWI/SNF chromatin remodeling complex, whose function is of critical importance in transcriptional regulation, contains approximately 10 protein components. The expression levels of the core SWI/SNF subunits, including BRG1/Brm, BAF155, BAF170, BAF60, hSNF/Ini1, and BAF57, are stoichiometric, with few to no unbound molecules in the cell. Here we report that exogenous expression of the wild type or certain deletion mutants of BAF57, a key subunit that mediates the interaction between the remodeling complex and transcription factors, results in diminished expression of endogenous BAF57. This down-regulation process is mediated by an increase in proteasome-dependent degradation of the BAF57 protein. Furthermore, the protein levels of BAF155/170 dictate the maximum cellular amount of BAF57. We mapped the domains responsible for the interaction between BAF57 and BAF155 and demonstrated that protein-protein interactions between them play an important role in this regulatory process. These findings provide insights into the physiological mechanisms responsible for maintaining the proper stoichiometric levels of the protein components comprising multimeric enzyme complexes.

scholarly journals A Specificity and Targeting Subunit of a Human SWI/SNF Family-Related Chromatin-Remodeling Complex

2000 ◽  
Vol 20 (23) ◽  
pp. 8879-8888 ◽  
Author(s):  
Zuqin Nie ◽  
Yutong Xue ◽  
Dafeng Yang ◽  
Sharleen Zhou ◽  
Bonnie J. Deroo ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Chromatin Remodeling ◽  
Protein Interactions ◽  
Transcriptional Activation ◽  
Gene Activation ◽  
Dna Interaction ◽  
Protein Protein Interactions ◽  
Baf Complex ◽  
Chromatin Remodeling Complexes

ABSTRACT The SWI/SNF family of chromatin-remodeling complexes facilitates gene activation by assisting transcription machinery to gain access to targets in chromatin. This family includes BAF (also called hSWI/SNF-A) and PBAF (hSWI/SNF-B) from humans and SWI/SNF and Rsc fromSaccharomyces cerevisiae. However, the relationship between the human and yeast complexes is unclear because all human subunits published to date are similar to those of both yeast SWI/SNF and Rsc. Also, the two human complexes have many identical subunits, making it difficult to distinguish their structures or functions. Here we describe the cloning and characterization of BAF250, a subunit present in human BAF but not PBAF. BAF250 contains structural motifs conserved in yeast SWI1 but not in any Rsc components, suggesting that BAF is related to SWI/SNF. BAF250 is also a homolog of the Drosophila melanogaster Osa protein, which has been shown to interact with a SWI/SNF-like complex in flies. BAF250 possesses at least two conserved domains that could be important for its function. First, it has an AT-rich DNA interaction-type DNA-binding domain, which can specifically bind a DNA sequence known to be recognized by a SWI/SNF family-related complex at the β-globin locus. Second, BAF250 stimulates glucocorticoid receptor-dependent transcriptional activation, and the stimulation is sharply reduced when the C-terminal region of BAF250 is deleted. This region of BAF250 is capable of interacting directly with the glucocorticoid receptor in vitro. Our data suggest that BAF250 confers specificity to the human BAF complex and may recruit the complex to its targets through either protein-DNA or protein-protein interactions.

scholarly journals Downstream and Intermediate Interactions of Synovial Sarcoma-Associated Fusion Oncoproteins and Their Implication for Targeted Therapy

Sarcoma ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Joanna Przybyl ◽  
Monika Jurkowska ◽  
Piotr Rutkowski ◽  
Maria Debiec-Rychter ◽  
Janusz A. Siedlecki
Keyword(s):  
Cell Proliferation ◽  
Targeted Therapy ◽  
Synovial Sarcoma ◽  
Chromatin Remodeling ◽  
Protein Interactions ◽  
Fusion Proteins ◽  
Soft Tissue Tumor ◽  
Fusion Genes ◽  
Protein Protein Interactions ◽  
Tp53 Pathway

Synovial sarcoma (SS), an aggressive type of soft tissue tumor, occurs mostly in adolescents and young adults. The origin and molecular mechanism of the development of SS remain only partially known. Over 90% of SS cases are characterized by the t(X;18)(p11.2;q11.2) translocation, which results mainly in the formation ofSS18-SSX1orSS18-SSX2fusion genes. In recent years, several reports describing direct and indirect interactions ofSS18-SSX1/SSX2oncoproteins have been published. These reports suggest that the fusion proteins particularly affect the cell growth, cell proliferation, TP53 pathway, and chromatin remodeling mechanisms, contributing to SS oncogenesis. Additional research efforts are required to fully explore the protein-protein interactions of SS18-SSX oncoproteins and the pathways that are regulated by these partnerships for the development of effective targeted therapy.

scholarly journals Novel functional insights revealed by distinct protein-protein interactions of the residual SWI/SNF complex in SMARCA4-deficient small cell carcinoma of the ovary, hypercalcemic type

2019 ◽  
Author(s):  
Elizabeth A. Raupach ◽  
Krystine Garcia-Mansfield ◽  
Ritin Sharma ◽  
Apurva M. Hegde ◽  
Victoria David-Dirgo ◽  
...  
Keyword(s):  
Cell Lines ◽  
Chromatin Remodeling ◽  
Protein Interactions ◽  
Rna Processing ◽  
Small Cell ◽  
Wild Type ◽  
Protein Protein Interactions ◽  
Functional Consequences ◽  
Carcinoma Of The Ovary ◽  
Inactivating Mutations

AbstractChromatin remodeling plays a critical role in tumor suppression as demonstrated by 20% of human cancers bearing inactivating mutations in SWI/SNF chromatin remodeling complex members. Mutations in different SWI/SNF subunits drive a variety of adult and pediatric tumor types, including non-small cell lung cancers, rhabdoid tumors, medulloblastomas, and ovarian cancers. Small cell carcinoma of the ovary hypercalcemic type (SCCOHT) is an aggressive subtype of ovarian cancer occurring in young women. Nearly all (>98%) SCCOHTs have inactivating mutations in SMARCA4, which encodes 1 of 2 mutually exclusive catalytic subunits of the SWI/SNF complex. Less than half of SCCOHT patients survive 5 years despite aggressive surgery and multimodal chemotherapy. Empirical support for effective SCCOHT treatments is scarce, in part because of the poor understanding of SCCOHT tumorigenesis. To gain insight into the functional consequences of SWI/SNF subunit loss, we defined SWI/SNF composition and its protein-protein interactions (PPIs) by immunoprecipitation and mass spectrometry (IP-MS) of SWI/SNF subunits in 3 SCCOHT cell lines. Comparing these results to a cell line containing a wild-type SWI/SNF complex, the interaction of most canonical core SWI/SNF subunits was observed in all SCCOHT cell lines at a lower abundance. The SCCOHT SWI/SNF also lacked ATPase module subunits and showed a drastic reduction in PBAF-specific subunit interactions. The wild-type and SCCOHT SWI/SNF subunits immunoprecipitated a shared set of 26 proteins, including core SWI/SNF subunits and RNA processing proteins. We observed 131 proteins exclusively interacting with the wild-type SWI/SNF complex including isoform-specific SWI/SNF subunits, members of the NuRD complex, and members of the MLL3/4 complex. We observed 60 PPIs exclusive to the SCCOHT residual SWI/SNF shared in at least 2 of the 3 SCCOHT cell lines, including many proteins involved in RNA processing. Differential interactions with the residual SWI/SNF complex in SCCOHT may further elucidate altered functional consequences of SMARCA4 mutations in these tumors as well as identify synthetic lethal targets that translate to other SWI/SNF-deficient tumors.

scholarly journals Screening for Inhibitors of an Essential Chromatin Remodeler in Mouse Embryonic Stem Cells by Monitoring Transcriptional Regulation

2012 ◽  
Vol 17 (9) ◽  
pp. 1221-1230 ◽  
Author(s):  
Emily C. Dykhuizen ◽  
Leigh C. Carmody ◽  
Nicola Tolliday ◽  
Gerald R. Crabtree ◽  
Michelle A. J. Palmer
Keyword(s):  
Chromatin Remodeling ◽  
Protein Interactions ◽  
Target Genes ◽  
Es Cells ◽  
Embryonic Stem ◽  
Diversity Oriented Synthesis ◽  
Qrt Pcr ◽  
Chromatin Remodeling Complex ◽  
Successful Approach ◽  
Polymerase Chain

The SWI/SNF-like adenosine triphosphate (ATP)–dependent chromatin remodeling complex, esBAF, is both necessary and, in some contexts, sufficient to induce the pluripotent state. Furthermore, mutations in various BAF subunits are associated with cancer. Little is known regarding the precise mechanism(s) by which this complex exerts its activities. Thus, it is unclear which protein interactions would be important to disrupt to isolate a relevant readout of mechanism. To address this, we developed a gene expression–based assay to identify inhibitors of the native esBAF complex. Specifically, a quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assay was developed in mouse embryonic stem (ES) cells to monitor expression of Bmi1, a developmentally important gene repressed by the esBAF complex. The assay was miniaturized to a 384-well format and used to screen a diverse collection of compounds, including novel products of diversity-oriented synthesis (DOS). Confirmed hits were validated using a knock-in ES cell reporter line in which luciferase is inserted into the Bmi1 locus. Several of the validated hits regulate a panel of target genes in a manner similar to the BAF chromatin-remodeling complex. Together these data indicate that expression-based screening using qRT-PCR is a successful approach to identify compounds targeting the regulation of key developmental genes in ES cells.

scholarly journals Methyl-CpG-binding domain 9 (MBD9) is required for H2A.Z incorporation into chromatin at a subset of H2A.Z-enriched regions in the Arabidopsis genome

2018 ◽  
Author(s):  
Paja Sijacic ◽  
Dylan H. Holder ◽  
Marko Bajic ◽  
Roger B. Deal
Keyword(s):  
Arabidopsis Thaliana ◽  
Chromatin Remodeling ◽  
Potential Role ◽  
Affinity Purification ◽  
Binding Domain ◽  
Tandem Affinity Purification ◽  
Related Protein ◽  
Single Mutant ◽  
Chromatin Remodeling Complex ◽  
Associated Proteins

ABSTRACTThe SWR1 chromatin remodeling complex, which deposits the histone variant H2A.Z into nucleosomes, has been characterized in yeast and animals but had not been purified from plants. We used the conserved SWR1 subunit ACTIN RELATED PROTEIN 6 (ARP6) as bait in tandem affinity purification experiments to isolate associated proteins from Arabidopsis thaliana. We identified all 11 subunits found in yeast SWR1 and the homologous mammalian SRCAP complexes, demonstrating that this complex is conserved in plants. We also identified several additional proteins not previously associated with SWR1, including Methyl-CpG-BINDING DOMAIN 9 (MBD9). Since mbd9 mutant plants were phenotypically similar to arp6 mutants, we further explored a potential role for MBD9 in H2A.Z deposition. We found that MBD9 is required for proper H2A.Z incorporation at thousands of discrete sites, which represent a subset of the regions normally enriched with H2A.Z. Genetic analyses showed that arp6;mbd9 double mutants have far more severe phenotypes than either single mutant. In conjunction with the finding that MBD9 does not appear to be a core subunit of the Arabidopsis SWR1 complex, this suggests that MBD9 also has important roles beyond H2A.Z deposition. Our data establish the SWR1 complex as being conserved across eukaryotes and also provide new insights into the mechanisms that target H2A.Z to chromatin.

Protein-protein interactions of the p53 family with the Bcl-2 family in hepatocellular carcinoma

2011 ◽  
Vol 49 (08) ◽  
Author(s):  
LC König ◽  
M Meinhard ◽  
C Sandig ◽  
MH Bender ◽  
A Lovas ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Protein Interactions ◽  
Protein Protein Interactions ◽  
P53 Family
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