A genome-wide RNAi screen identifies MASK as a positive regulator of cytokine receptor stability
| Autor: | Katherine H. Fisher, Martin P. Zeidler, Maria A. Arredondo, Dhamayanthi Pugazhendhi, Stephen Brown, Maria Fragiadaki, Nina Bausek, Sally Thomas |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Amino Acid Motifs Genome Insect Regulator Biology stat 03 medical and health sciences 0302 clinical medicine Animals Drosophila Proteins Humans Receptors Cytokine Receptor Tissue homeostasis Janus Kinases Protein Stability RNA-Binding Proteins JAK-STAT signaling pathway Receptors Interleukin Cell Biology Cell biology DNA-Binding Proteins STAT Transcription Factors Drosophila melanogaster 030104 developmental biology Gene Expression Regulation STAT protein RNA Interference Janus kinase Cytokine receptor 030217 neurology & neurosurgery Research Article Protein Binding Signal Transduction |
| Zdroj: | Journal of Cell Science. |
| ISSN: | 1477-9137 0021-9533 |
| Popis: | Cytokine receptors often act via the Janus kinase and signal transducer and activator of transcription (JAK/STAT) pathway to form a signalling cascade that is essential for processes such as haematopoiesis, immune responses and tissue homeostasis. In order to transduce ligand activation, cytokine receptors must dimerise. However, mechanisms regulating their dimerisation are poorly understood. In order to better understand the processes regulating cytokine receptor levels, and their activity and dimerisation, we analysed the highly conserved JAK/STAT pathway in Drosophila , which acts via a single receptor, known as Domeless. We performed a genome-wide RNAi screen in Drosophila cells, identifying MASK as a positive regulator of Domeless dimerisation and protein levels. We show that MASK is able to regulate receptor levels and JAK/STAT signalling both in vitro and in vivo . We also show that its human homologue, ANKHD1, is also able to regulate JAK/STAT signalling and the levels of a subset of pathway receptors in human cells. Taken together, our results identify MASK as a novel regulator of cytokine receptor levels, and suggest functional conservation, which may have implications for human health. This article has an associated First Person interview with the first author of the paper. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|