University of Oulu

Järvelä-Stölting M, Vesala L, Maasdorp MK, Ciantar J, Rämet M and Valanne S (2021) Proteasome α6 Subunit Negatively Regulates the JAK/STAT Pathway and Blood Cell Activation in Drosophila melanogaster. Front. Immunol. 12:729631. doi: 10.3389/fimmu.2021.729631

Proteasome α6 subunit negatively regulates the JAK/STAT pathway and blood cell activation in Drosophila melanogaster

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Author: Järvelä-Stölting, Mirva1; Vesala, Laura1; Maasdorp, Matthew K.1;
Organizations: 1Laboratory of Experimental Immunology, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
2Research Unit for Pediatrics, Pediatric Neurology, Pediatric Surgery, Child Psychiatry, Dermatology, Clinical Genetics, Obstetrics and Gynecology, Otorhinolaryngology and Ophthalmology, Faculty of Medicine, University of Oulu, Oulu, Finland
3Medical Research Center Oulu, University of Oulu, Oulu, Finland
4Department of Children and Adolescents, Oulu University Hospital, University of Oulu, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 4.5 MB)
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Language: English
Published: Frontiers Media, 2021
Publish Date: 2022-02-22


JAK/STAT signaling regulates central biological functions such as development, cell differentiation and immune responses. In Drosophila, misregulated JAK/STAT signaling in blood cells (hemocytes) induces their aberrant activation. Using mass spectrometry to analyze proteins associated with a negative regulator of the JAK/STAT pathway, and by performing a genome-wide RNAi screen, we identified several components of the proteasome complex as negative regulators of JAK/STAT signaling in Drosophila. A selected proteasome component, Prosα6, was studied further. In S2 cells, Prosα6 silencing decreased the amount of the known negative regulator of the pathway, ET, leading to enhanced expression of a JAK/STAT pathway reporter gene. Silencing of Prosα6 in vivo resulted in activation of the JAK/STAT pathway, leading to the formation of lamellocytes, a specific hemocyte type indicative of hemocyte activation. This hemocyte phenotype could be partially rescued by simultaneous knockdown of either the Drosophila STAT transcription factor, or MAPKK in the JNK-pathway. Our results suggest a role for the proteasome complex components in the JAK/STAT pathway in Drosophila blood cells both in vitro and in vivo.

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Series: Frontiers in immunology
ISSN: 1664-3224
ISSN-E: 1664-3224
ISSN-L: 1664-3224
Volume: 12
Article number: 729631
DOI: 10.3389/fimmu.2021.729631
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
3111 Biomedicine
Funding: This work was supported by the Tampere University Doctoral Programme in Medicine and Life Sciences and The Finnish Cultural Foundation (to MJ-S); The Sigrid Juselius Foundation, the Academy of Finland (Grant 277495), the Competitive State Research Financing of the Expert Responsibility Area of Oulu University Hospital and the Tampere Tuberculosis Foundation (to MR); and the Tuberculosis foundation (to SV). The Tampere Drosophila Facility, the Tampere Imaging Facility and the Tampere Facility of Flow Cytometry are all partially funded by Biocenter Finland.
Copyright information: © 2021 Järvelä-Stölting, Vesala, Maasdorp, Ciantar, Rämet and Valanne. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.