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61.
G protein-coupled receptors (GPCRs) are critical players in tumor growth and progression. The redundant roles of GPCRs in tumor development confound effective treatment; therefore, targeting a single common signaling component downstream of these receptors may be efficacious. GPCRs transmit signals through heterotrimeric G proteins composed of Gα and Gβγ subunits. Hyperactive Gαs signaling can mediate tumor progression in some tissues; however, recent work in medulloblastoma and basal cell carcinoma revealed that Gαs can also function as a tumor suppressor in neoplasms derived from ectoderm cells including neural and epidermal stem/progenitor cells. In these stem-cell compartments, signaling through Gαs suppresses self-renewal by inhibiting the Sonic Hedgehog (SHH) and Hippo pathways. The loss of GNAS, which encodes Gαs, leads to activation of these pathways, over-proliferation of progenitor cells, and tumor formation. Gαs activates the cAMP-dependent protein kinase A (PKA) signaling pathway and inhibits activation of SHH effectors Smoothened-Gli. In addition, Gαs-cAMP-PKA activation negatively regulates the Hippo pathway by blocking the NF2-LATS1/2-Yap signaling. In this review, we will address the novel function of the signaling network regulated by Gαs in suppression of SHH-driven tumorigenesis and the therapeutic approaches that can be envisioned to harness this pathway to inhibit tumor growth and progression. 相似文献
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Zafar Rukhsar Chauhan Pooja Salim Mohammad Singh Ghanshyam 《Plasmonics (Norwell, Mass.)》2019,14(4):1013-1017
Plasmonics - Photonics provides a key solution to limit the myriads of challenges offered by existing silicon technology. Here, we propose a simple 2-channel Plasmonic demultiplexer with... 相似文献
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Parth R. Chauhan 《The journal of the Royal Anthropological Institute》2019,25(4):850-851
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Kriti Chopra Shrankhla Bawaria Radha Chauhan 《Protein science : a publication of the Protein Society》2019,28(3):571-586
Nuclear pore complex (NPC) is the largest multimeric protein assembly of the eukaryotic cell, which mediates the nucleocytoplasmic transport. The constituent proteins of this assembly (nucleoporins) are present in varying copy numbers to give a size from ~ 60 MDa (yeast) to 112 MDa (human) and share common ancestry with other membrane‐associated complexes such as COPI/COPII and thus share the same structural folds. However, the nucleoporins across species exhibit very low percentage sequence similarity and this reflects in their distinct secondary structure and domain organization. We employed thorough sequence and phylogenetic analysis guided from structure‐based alignments of all the nucleoporins from fungi to metazoans to understand the evolution of NPC. Through evolutionary pressure analysis on various nucleoporins, we deduced that these proteins are under differential selection pressure and hence the homologous interacting partners do not complement each other in the in vitro pull‐down assay. The super tree analysis of all nucleoporins taken together illustrates divergent evolution of nucleoporins and notably, the degree of divergence is more apparent in higher order organisms as compared to lower species. Overall, our results support the hypothesis that the protein–protein interactions in such large multimeric assemblies are species specific in nature and hence their structure and function should also be studied in an organism‐specific manner. 相似文献
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Das Abhijit Kumar Jaiswal Sunil Kumar Muthusamy Vignesh Zunjare Rajkumar Uttamrao Chauhan Hema Singh Chand Gulab Saha Supradip Hossain Firoz 《Journal of plant biochemistry and biotechnology.》2019,28(3):253-262
Journal of Plant Biochemistry and Biotechnology - Vitamin E deficiency is a serious health concern in humans. Biofortification of maize kernel with high vitamin E (α-tocopherol) provides... 相似文献
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Kaustuv Basu Nancy Maurya Jasbir Kaur Rohit Saxena Viney Gupta Ramanjit Sihota Ilora Ghosh 《Cell biology international》2019,43(7):820-834
The pathological mechanism underlying glaucoma has always been a complex aspect of this permanently blinding disease but proteomic studies have been helpful in elucidating it to a great extent in several studies. This study was designed to evaluate the expression and to get an idea about the function of two novel markers (ligatin and fibulin‐7) identified in human aqueous humor (hAH) in relation to glaucomatous progression. A significant increase in the protein content of glaucomatous hAH compared to that of non‐glaucomatous controls (NG‐Ctrls) was observed. Ligatin, fibulin‐7, and its proteolysis were revealed in hAH of primary open angle glaucoma (POAG), primary angle closure glaucoma (PACG) and NG‐Ctrls. Quantification confirmed no significant difference in expression of ligatin, whereas fibulin‐7 was significantly (P < 0.05) low in hAH of PACG in comparison to NG‐Ctrls and POAG. Importantly the immunohistochemical assay for both indicated their possible involvement in the maintenance of the appropriate structure of TM in vivo. Since oxidative stress is a major contributor to glaucomatous pathogenesis, in vitro analysis of nuclear and cytoplasmic fractions indicated intracellular changes in localization and expression of ligatin upon oxidative insult of human trabecular meshwork (TM) cells. While no such changes were found for fibulin‐7 expression. This was also corroborated with the immunocytochemical assay. Though a study with a small sample size, this is the first report which confirms the presence of ligatin and fibulin‐7 in hAH, quantified their differential expression, and indicated the possibility of their involvement in the maintenance of the TM structure. 相似文献
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