Müller, P., Pugazhendhi, D. and Zeidler, M. P. (2012) Modulation of human JAK-STAT pathway signaling by functionally conserved regulators. JAK-STAT, 1 (1). pp. 34-43. ISSN 2162-3988
Abstract
Both the core JAK-STAT pathway components and their in vivo roles have been widely conserved between vertebrates and invertebrate models such as Drosophila melanogaster. Misregulation of JAK-STAT pathway activity has also been identified as a key factor in the development of multiple human malignancies. Recently, whole genome RNA interference (RNAi) screens in cultured Drosophila cells have identified both positively and negatively acting JAK-STAT pathway regulators. Here, we describe the analysis of 73 human genes representing homologs of 56 Drosophila genes originally identified by genome-wide RNAi screening as regulators of JAK-STAT signaling. Using assays for human STAT1 and STAT3 protein levels and phosphorylation status, as well as assays measuring the expression of endogenous STAT1 and STAT3 transcriptional targets, we have tested siRNAs targeting these 73 human genes and have identified potential JAK-STAT pathway regulatory roles in 69 (95%) of these. The genes identified represent a wide range of human JAK-STAT pathway regulators and include genes not previously known to modulate this signaling cascade. These results underline the value of model system based approaches for the identification of pathway regulators and have led to the identification of loci whose misregulation may ultimately be implicated in JAK-STAT pathway-mediated human disease.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2012 Landes Bioscience This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited. https://creativecommons.org/licenses/by-nc/3.0/ |
Keywords: | assay; Drosophila; GBP1; HeLa; phosphorylation; RNAi; screening; SOCS3 |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Biomedical Science (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 21 Mar 2017 16:08 |
Last Modified: | 21 Mar 2017 16:08 |
Published Version: | http://dx.doi.org/10.4161/jkst.18006 |
Status: | Published |
Publisher: | Taylor & Francis: STM, Behavioural Science and Public Health Titles |
Refereed: | Yes |
Identification Number: | 10.4161/jkst.18006 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:113785 |