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991.
992.
Evgenia Gubanova Natalia Issaeva Camilla Gokturk Tatjana Djureinovic Thomas Helleday 《Cell cycle (Georgetown, Tex.)》2013,12(24):3770-3780
The DNA damage response is coordinated by phosphatidylinositol 3-kinase-related kinases, ATM, ATR, and DNA-PK. SMG-1 is the least studied stress-responsive member of this family. Here, we show that SMG-1 regulates the G1/S checkpoint through both a p53-dependent, and a p53-independent pathway. We identify Cdc25A as a new SMG-1 substrate, and show that cells depleted of SMG-1 exhibit prolonged Cdc25A stability, failing to inactivate CDK2 in response to radiation. Given an increased tumor growth following depletion of SMG-1, our data demonstrate a novel role for SMG-1 in regulating Cdc25A and suppressing oncogenic CDK2 driven proliferation, confirming SMG-1 as a tumor suppressor. 相似文献
993.
We compared immunohistochemical (IHC) staining of tissue sections of liver, kidney, spleen, lung, proventriculus, sciatic nerve, bursa of Fabricius, brain, heart, intestine and skin; immunocytochemical (ICC) staining of peripheral blood samples and touch preparations of liver, spleen and kidney of laying hens naturally infected with Marek’s disease (MD) virus. We used one hundred and fifty 5-17-week-old commercial hens. IHC and ICC staining were performed using polymer-based techniques. IHC staining exhibited mostly free immunopositive reactions in tumor cells and in the cytoplasm of the parenchymal cells of liver, kidney, spleen and bursa of Fabricius. In the sciatic nerve, severe reactions were observed in the cytoplasm of plasma and MD cells in the lymphoproliferative areas. Pronounced staining was found in the lymphoid cells in the medulla of intrafollicular regions in the bursa of Fabricius. Although immunostaining was observed in the liver and spleen touch preparations, there was no staining in the kidneys and peripheral blood cell samples. The presence of virus in the tissue and peripheral blood samples and in touch preparations was compared immunohistochemically and immunocytochemically. IHC and ICC techniques were helpful for diagnosis of MD. Peripheral blood samples are inappropriate for field conditions and natural infections. 相似文献
994.
《Developmental cell》2022,57(10):1226-1240.e8
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995.
CXCR6 positions cytotoxic T cells to receive critical survival signals in the tumor microenvironment
《Cell》2021,184(17):4512-4530.e22
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996.
Robert Cheng Brunella Felicetti Shilpa Palan Ian Toogood‐Johnson Christoph Scheich John Barker Mark Whittaker Thomas Hesterkamp 《Protein science : a publication of the Protein Society》2010,19(1):168-173
The Mapkap kinases 2 and 3 (MK2 and MK3) have been implicated in intracellular signaling pathways leading to the production of the pro‐inflammatory cytokine tumor necrosis factor alpha. MK2 has been pursued by the biopharmaceutical industry for many years for the development of a small molecule anti‐inflammatory treatment and drug‐like inhibitors have been described. The development of some of these compounds, however, has been slowed by the absence of a high‐resolution crystal structure of MK2. Herein we present a high‐resolution (1.9 Å) crystal structure of the highly homologous MK3 in complex with a pharmaceutical lead compound. While all of the canonical features of Ser/Thr kinases in general and MK2 in particular are recapitulated in MK3, the detailed analysis of the binding interaction of the drug‐like ligand within the adenine binding pocket allows relevant conclusions to be drawn for the further design of potent and selective drug candidates. 相似文献
997.
James R. Byrnes Amy M. Weeks Eric Shifrut Julia Carnevale Lisa Kirkemo Alan Ashworth Alexander Marson James A. Wells 《Molecular & cellular proteomics : MCP》2022,21(4):100217
Immunosuppressive factors in the tumor microenvironment (TME) impair T cell function and limit the antitumor immune response. T cell surface receptors and surface proteins that influence interactions and function in the TME are proven targets for cancer immunotherapy. However, how the entire surface proteome remodels in primary human T cells in response to specific suppressive factors in the TME remains to be broadly and systematically characterized. Here, using a reductionist cell culture approach with primary human T cells and stable isotopic labeling with amino acids in cell culture–based quantitative cell surface capture glycoproteomics, we examined how two immunosuppressive TME factors, regulatory T cells (Tregs) and hypoxia, globally affect the activated CD8+ surface proteome (surfaceome). Surprisingly, coculturing primary CD8+ T cells with Tregs only modestly affected the CD8+ surfaceome but did partially reverse activation-induced surfaceomic changes. In contrast, hypoxia drastically altered the CD8+ surfaceome in a manner consistent with both metabolic reprogramming and induction of an immunosuppressed state. The CD4+ T cell surfaceome similarly responded to hypoxia, revealing a common hypoxia-induced surface receptor program. Our surfaceomics findings suggest that hypoxic environments create a challenge for T cell activation. These studies provide global insight into how Tregs and hypoxia remodel the T cell surfaceome and we believe represent a valuable resource to inform future therapeutic efforts to enhance T cell function. 相似文献
998.
《Journal of receptor and signal transduction research》2013,33(1):49-55
AbstractBackground: Tumor necrosis factor (TNF)-α is an inflammatory cytokine, the biological effects of which are mediated by the interaction with specific membrane-bound receptors. To assess TNF-α receptor (TNFR) expression, it is important to estimate both the number of cells that carry these receptors and the number of receptors per cell, because the cell fate depends on the balance between TNFRI and TNFRII signaling. Objective: The aim of the present study was to develop an optimized protocol to estimate the level of expression of membrane-bound TNFRI and TNFRII, using QuantiBRITE PE calibration beads. Materials and methods: The percentage of cells that expressed membrane-bound TNFRI and TNFRII and the mean number of receptors per cell were determined by flow cytometry using PE-labeled antibodies against TNFR. To create a calibration curve and convert cell fluorescence intensity values to absolute numbers of receptors, we used QuantiBRITE PE beads. Results: CD19+ B lymphocytes had the least percentage of cells expressing TNFRI and the greatest number of receptor molecules per cell, whereas CD3+ T lymphocytes had the greatest percentage of cells expressing TNFRII and the lowest density of these receptors. We also established that stimulation of peripheral blood mononuclear cells (PBMCs) with the lipopolysaccharide (LPS) significantly increased the number of TNFRI and TNFRII on CD14+ monocytes. Conclusion: Application of the protocol-identified differences in the percentage of cells that expressed TNFRs, as well as the absolute number of receptors per cell, among different subpopulations of PBMCs, and between PBMCs cultured with and without LPS. 相似文献
999.
Woo Suk Choi Bochao Liu Zhiyuan Shen Wei Yang 《Protein science : a publication of the Protein Society》2021,30(3):693
BCCIP was isolated based on its interactions with tumor suppressors BRCA2 and p21. Knockdown or knockout of BCCIP causes embryonic lethality in mice. BCCIP deficient cells exhibit impaired cell proliferation and chromosome instability. BCCIP also plays a key role in biogenesis of ribosome 60S subunits. BCCIP is conserved from yeast to humans, but it has no discernible sequence similarity to proteins of known structures. Here we report two crystal structures of an N‐terminal truncated human BCCIPβ, consisting of residues 61–314. Structurally BCCIP is similar to GCN5‐related acetyltransferases (GNATs) but contains different sequence motifs. Moreover, both acetyl‐CoA and substrate‐binding grooves are altered in BCCIP. A large 19‐residue flap over the putative CoA binding site adopts either an open or closed conformation in BCCIP. The substrate binding groove is significantly reduced in size and is positively charged despite the acidic isoelectric point of BCCIP. BCCIP has potential binding sites for partner proteins and may have enzymatic activity. 相似文献
1000.