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5 results for “GRK5”
Global Functional Genomics Reveals GRK5 as a Therapeutic Target for Cystic Fibrosis
<p>Cystic Fibrosis (CF) is a life-shortening disease affecting >90,000 individuals worldwide predominantly with respiratory symptoms. About 80% of individuals with CF have the F508del mutation that causes the CF transmembrane conductance regulator (CFTR) protein to misfold and be targeted for premature degradation by the endoplasmic reticulum (ER) quality control (ERQC), thus preventing its plasma membrane (PM) traffic. Despite the recent approval of a ‘highly effective’ drug rescuing F508del-CFTR, maximal lung function improvement is ~14% and the drug-targeted genes remain unknown.</p> <p>To identify global modulators of F508del traffic, we performed a high-content siRNA microscopy-based screen of >9,000 genes and monitored F508del-CFTR PM rescue in human airway cells. This primary screen identified 227 F508del-CFTR traffic regulators, of which 35 could be validated by additional siRNAs. Subsequent mechanistic studies established GRK5 as a robust regulator whose inhibition rescues F508del-CFTR PM traffic, thus emerging as a novel potential drug target for CF.</p>
"Global Functional Genomics Reveals GRK5 as a Therapeutic Target for Cystic Fibrosis", CFTR interactomes
<p><em>A tidy selection of published CFTR interactomes (or CFTR-related omics datasets)</em></p> <p>Collects data from the original online sources, converts gene/protein identifiers into a standard tidy format and updates the identifiers. The Uniprot ID is taken as reference and all other identifiers are genereated from them. This causes some datasets to end up with less genes/proteins than reported.</p> <p>Datasets included</p> <ul> <li><strong>Botelho (2021)</strong> - CFTR traffic regulators <ul> <li>Botelho <em>et al</em> (2022), submitted</li> </ul> </li> <li><strong>Pankow (2015)</strong> - CFTR interactome <ul> <li>Pankow <em>et al</em> (2015) deltaF508 CFTR interactome remodelling promotes rescue of cystic fibrosis. <em>Nature</em>. 528, 510--516. <a href="https://doi.org/10.1038/nature15729">https://doi.org/10.1038/nature15729</a></li> </ul> </li> <li><strong>Canato (2018)</strong> - CFTR interactome <ul> <li>Canato <em>et al</em> (2018) Proteomic interaction profiling reveals KIFC1 as a factor involved in early targeting of F508del-CFTR to degradation. <em>Cell Mol Life Sci</em>. 75(24):4495-4509. <a href="https://doi.org/10.1007/s00018-018-2896-7">https://doi.org/10.1007/s00018-018-2896-7</a></li> </ul> </li> <li><strong>Santos (2019)</strong> - CFTR interactome <ul> <li>Santos <em>et al</em> (2019) Folding Status Is Determinant over Traffic-Competence in Defining CFTR Interactors in the Endoplasmic Reticulum. <em>Cells</em>. 8(4):353. <a href="https://doi.org/10.3390/cells8040353">https://doi.org/10.3390/cells8040353</a></li> </ul> </li> <li><strong>Hutt (2018)</strong> - CFTR interactome <ul> <li>Hutt <em>et al</em> (2018) A Proteomic Variant Approach (ProVarA) for Personalized Medicine of Inherited and Somatic Disease. <em>J Mol Biol</em>. 430: 2951-2973. <a href="https://doi.org/10.1016/j.jmb.2018.06.017">https://doi.org/10.1016/j.jmb.2018.06.017</a></li> </ul> </li> <li><strong>Rauniyar (2014)</strong> - CFTR proteome <ul> <li>Rauniyar <em>et al</em> (2014) Quantitative Proteomic Profiling Reveals Differentially Regulated Proteins in Cystic Fibrosis Cells. <em>J Proteome Res</em>. 13(11): 4668-4675. <a href="https://doi.org/10.1021/pr500370g">https://doi.org/10.1021/pr500370g</a></li> </ul> </li> <li><strong>Almaça (2013)</strong> - ENaC regulome <ul> <li>Almaça <em>et al</em> (2013) High-content siRNA screen reveals global ENaC regulators and potential cystic fibrosis therapy targets. <em>Cell</em>. 154(6):1390-400. <a href="https://doi.org/10.1016/j.cell.2013.08.045">https://doi.org/10.1016/j.cell.2013.08.045</a></li> </ul> </li> <li><strong>Tomati (2018)</strong> - CFTR regulome <ul> <li>Tomati <em>et al</em> (2018) High-throughput screening identifies FAU protein as a regulator of mutant cystic fibrosis transmembrane conductance regulator channel. <em>J Biol Chem</em>. 293(4):1203-1217. <a href="https://doi.org/10.1074/jbc.m117.816595">https://doi.org/10.1074/jbc.m117.816595</a></li> </ul> </li> <li><strong>Simpson (2012)</strong> - Secretome <ul> <li>Simpson <em>et al</em> (2012) Genome-wide RNAi screening identifies human proteins with a regulatory function in the early secretory pathway. <em>Nature Cell Biology</em>. 14, 764-774. <a href="https://doi.org/10.1038/ncb2510">https://doi.org/10.1038/ncb2510</a></li> </ul> </li> <li><strong>Wang (2006)</strong> - CFTR interactome <ul> <li>Wang <em>et al</em> (2006) Hsp90 Cochaperone Aha1 Downregulation Rescues Misfolding of CFTR in Cystic Fibrosis. <em>Cell</em>. 127(4):803-815. <a href="https://doi.org/10.1016/j.cell.2006.09.043">https://doi.org/10.1016/j.cell.2006.09.043</a></li> </ul> </li> <li><strong>Reilly (2017)</strong> - CFTR interactome <ul> <li>Reilly <em>et al</em> (2017) Targeting the PI3K/Akt/mTOR signalling pathway in Cystic Fibrosis. <em>Sci Rep</em>. 9;7(1):7642. <a href="https://doi.org/10.1038/s41598-017-06588-z">https://doi.org/10.1038/s41598-017-06588-z</a></li> </ul> </li> <li><strong>Gilchrist (2006)</strong> - Secretome <ul> <li>Gilchrist <em>et al</em> (2006) Quantitative Proteomics Analysis of the Secretory Pathway. <em>Cell</em>. 127(6):1265-1281. <a href="https://doi.org/10.1016/j.cell.2006.10.036">https://doi.org/10.1016/j.cell.2006.10.036</a></li> </ul> </li> <li><strong>Pankow (2019)</strong> - CFTR interactome <ul> <li>Pankow <em>et al</em> (2019) A posttranslational modification code for CFTR maturation is altered in cystic fibrosis. <em>Science Signaling</em>. 12(562):eaan7984. <a href="https://doi.org/10.1126/scisignal.aan7984">https://doi.org/10.1126/scisignal.aan7984</a></li> </ul> </li> <li><strong>Dang (2020)</strong> - CF lung disease modifier genes <ul> <li>Dang <em>et al</em> (2020) Mining GWAS and eQTL data for CF lung disease modifiers by gene expression imputation. <em>PLoS One</em>. 15(11):e0239189. <a href="https://doi.org/10.1371/journal.pone.0239189">https://doi.org/10.1371/journal.pone.0239189</a></li> </ul> </li> <li><strong>Hodos (2020)</strong> - CF genomic meta-analysis <ul> <li>Hodos <em>et al</em> (2020) Integrative genomic meta-analysis reveals novel molecular insights into cystic fibrosis and deltaF508-CFTR rescue. <em>Sci Rep</em> 10(1):20553. <a href="http://dx.doi.org/10.1038/s41598-020-76347-0">http://dx.doi.org/10.1038/s41598-020-76347-0</a></li> </ul> </li> </ul>
Cand2 links pathological mTORC1 signaling to adverse cardiac remodeling by regulating Grk5 expression
GEO Series GSE153364. Mus musculus. 10 samples. Type: Expression profiling by high throughput sequencing.
Type 2 diabetes susceptibility gene GRK5 regulates physiological pancreatic β-cell proliferation via phosphorylation of HDAC5
GEO Series GSE221716. Mus musculus. 10 samples. Type: Expression profiling by high throughput sequencing.
KLF9-GRK5-HDAC6 axis aggravates osteoarthritis pathogenesis by promoting chondrocyte extracellular matrix degradation and apoptosis
GEO Series GSE285234. Homo sapiens. 12 samples. Type: Expression profiling by high throughput sequencing.
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International Brain Laboratory public data
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OpenNeuro
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