The transcription factor MYC binds specific DNA sites in cellular chromatin and induces the acetylation of histones H3 and H4. However, the histone acetyltransferases (HATs) that are responsible for ...these modifications have not yet been identified. MYC associates with TRRAP, a subunit of distinct macromolecular complexes that contain the HATs GCN5/PCAF or TIP60. Although the association of MYC with GCN5 has been shown, its interaction with TIP60 has never been analysed. Here, we show that MYC associates with TIP60 and recruits it to chromatin in vivo with four other components of the TIP60 complex: TRRAP, p400, TIP48 and TIP49. Overexpression of enzymatically inactive TIP60 delays the MYC‐induced acetylation of histone H4, and also reduces the level of MYC binding to chromatin. Thus, the TIP60 HAT complex is recruited to MYC‐target genes and, probably with other other HATs, contributes to histone acetylation in response to mitogenic signals.
Here, we report the identification of a new E1A binding protein complex that is essential for E1A-mediated transformation. Its core component is a SWI2/SNF2-related, 400 kDa protein (p400). Other ...components include the myc- and p/CAF-associated cofactor, TRRAP/PAF400, the DNA helicases TAP54α/β, actin-like proteins, and the human homolog of the
Drosophila Enhancer of Polycomb protein. An E1A mutant, defective in p400 binding, is also defective in transformation. Certain p400 fragments partially rescued this phenotype, underscoring the role of E1A-p400 complex formation in the E1A transforming process. Furthermore, E1A and c-
myc each alter the subunit composition of p400 complexes, implying that physiological p400 complex formation contributes to transformation suppression.
Battershill's most important resources are the Hogarth Press Business Archives (University of Reading, England); Monk's House Papers and The Leonard Woolf Papers (University of Sussex); the ...digitalized Modernist Archives Publishing Project; and additional holdings in the US and Canada. Working with data and correspondence from the original files, the author cites details on manuscript acquisitions, genre categorization, print runs, editions, pricing, marketing venues, book design, reviewing, and more. Battershill interweaves information from the archives with analyses of individual books in order to emphasize the variety of approaches and techniques.
Chimeric antigen receptor (CAR)‐T cell therapy is a new class of cellular immunotherapies that involves ex vivo genetic modification of T cells to incorporate an engineered CAR. After infusion into ...the patient, the CAR‐expressing T cells recognize specific tumor targets and induce an immune response against them. The technology utilized is fundamentally different from previously available cancer treatments. Currently, most CAR‐T cell therapies use autologous T cells. Tisagenlecleucel (formerly CTL019) is an anti‐CD19 CAR‐T cell therapy that was recently approved in the United States for the treatment of pediatric and young adult patients with relapsed/refractory B‐cell acute lymphoblastic leukemia (B‐ALL). Tisagenlecleucel has shown robust in vivo expansion and long‐term persistence, clinically meaningful durable response and remission rates, and overall survival benefit in pediatric and young adult patients with relapsed/refractory B‐ALL and in relapsed/refractory diffuse large B‐cell lymphoma. Common adverse events (AEs) include cytokine release syndrome, which may require hospitalization and admission to an intensive care unit, neurological toxicities, and B‐cell aplasia. These AEs are manageable when treated by an appropriately trained team. Additional research is required to further develop AE management protocols. In this review, we describe regulatory requirements, clinical considerations, and site‐level requirements for clinical study implementation of CAR‐T cell therapy in Europe. We also provide a case study of the European experience from the first global clinical trial for tisagenlecleucel, which may serve as a useful starting point for investigators and clinicians looking to implement CAR‐T cell therapy at their institutions.
Breaking the sequence Friedman, Ellen G; Friedman, Ellen G; Fuchs, Miriam
2014., 20140701, 2014, 1989, Letnik:
960
eBook
These nineteen essays introduce the rich and until now largely unexplored tradition of women's experimental fiction in the twentieth century. The writers discussed here range from Gertrude Stein to ...Christine Brooke-Rose and include, among others, Virginia Woolf, Jean Rhys, Jane Bowles, Marguerite Young, Eva Figes, Joyce Carol Oates, and Marguerite Duras. "Friedman and Fuchs demonstrate the breadth of their research, first in their introduction to the volume, in which they outline the history of the reception of women's experimental fiction, and analyze and categorize the work not only of the writers to whom essays are devoted but of a number of others, too; and second in an extensive and wonderfully useful bibliography."--Emma Kafalenos, The International Fiction Review "After an introduction that is practically itself a monograph, eighteen essayists (too many of them distinguished to allow an equitable sampling) take up three generations of post-modernists."--American Literature "The editors see this volume as part of the continuing feminist project of the `recovery and foregrounding of women writers.' Friedman and Fuchs's substantive introduction excellently synthesizes the issues presented in the rest of the volume."--Patrick D. Murphy, Studies in the Humanities
Originally published in 1992.
ThePrinceton Legacy Libraryuses the latest print-on-demand technology to again make available previously out-of-print books from the distinguished backlist of Princeton University Press. These paperback editions preserve the original texts of these important books while presenting them in durable paperback editions. The goal of the Princeton Legacy Library is to vastly increase access to the rich scholarly heritage found in the thousands of books published by Princeton University Press since its founding in 1905.
p400 Is Required for E1A to Promote Apoptosis Samuelson, Andrew V.; Narita, Masako; Chan, Ho-Man ...
Journal of biological chemistry/The Journal of biological chemistry,
06/2005, Letnik:
280, Številka:
23
Journal Article
Recenzirano
Odprti dostop
The adenovirus E1A oncoprotein promotes proliferation and transformation by binding cellular proteins, including members of the retinoblastoma protein family, the p300/CREB-binding protein ...transcriptional coactivators, and the p400-TRRAP chromatin-remodeling complex. E1A also promotes apoptosis, in part, by engaging the ARF-p53 tumor suppressor pathway. We show that E1A induces ARF and p53 and promotes apoptosis in normal fibroblasts by physically associating with the retinoblastoma protein and a p400-TRRAP complex and that its interaction with p300 is largely dispensable for these effects. We further show that E1A increases p400 expression and, conversely, that suppression of p400 using stable RNA interference reduces the levels of ARF, p53, and apoptosis in E1A-expressing cells. Therefore, whereas E1A inactivates the retinoblastoma protein, it requires p400 to efficiently promote cell death. These results identify p400 as a regulator of the ARF-p53 pathway and a component of the cellular machinery that couples proliferation to cell death.
The molecular chaperone GroE facilitates correct protein folding in vivo and in vitro. The mode of action of GroE was investigated by using refolding of citrate synthase as a model system. In vitro ...denaturation of this dimeric protein is almost irreversible, since the refolding polypeptide chains aggregate rapidly, as shown directly by a strong, concentration-dependent increase in light scattering. The yields of reactivated citrate synthase were strongly increased upon addition of GroE and MgATP. GroE inhibits aggregation reactions that compete with correct protein folding, as indicated by specific suppression of light scattering. GroEL rapidly forms a complex with unfolded or partially folded citrate synthase molecules. In this complex the refolding protein is protected from aggregation. Addition of GroES and ATP hydrolysis is required to release the polypeptide chain bound to GroEL and to allow further folding to its final, active state.
Abstract
The Submillimetre Common User Bolometer Array 2 (SCUBA-2) is the James Clerk Maxwell Telescope’s continuum imager, operating simultaneously at 450 and 850
μ
m. SCUBA-2 was commissioned in ...2009–2011, and since that time, regular observations of point-like standard sources have been performed whenever the instrument is in use. Expanding the calibrator observation sample by an order of magnitude compared to previous work, in this paper we derive updated opacity relations at each wavelength for a new atmospheric extinction correction, analyze the Flux Conversion Factors used to convert instrumental units to physical flux units as a function of date and observation time, present information on the beam profiles for each wavelength, and update secondary calibrator source fluxes. Between 07:00 and 17:00 UTC, the portion of the night that is most stable to temperature gradients that cause dish deformation, the total flux uncertainty and the peak flux uncertainty measured at 450
μ
m are found to be 14% and 17%, respectively. Measured at 850
μ
m, the total flux and peak flux uncertainties are 6% and 7%, respectively. The analysis presented in this work is applicable to all SCUBA-2 projects observed since 2011.
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