Interactome Networks of FOSL1 and FOSL2 in Human Th17 Cells

Ankitha Shetty, Santosh D. Bhosale, Subhash Kumar Tripathi, Tanja Buchacher, Rahul Biradar, Omid Rasool, Robert Moulder, Sanjeev Galande, Riitta Lahesmaa*

*Korresponderande författare för detta arbete

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

1 Citeringar (Scopus)
1 Nedladdningar (Pure)

Sammanfattning

Dysregulated function of Th17 cells has implications in immunodeficiencies and autoimmune disorders. Th17 cell differentiation is orchestrated by a complex network of transcription factors, including several members of the activator protein (AP-1) family. Among the latter, FOSL1 and FOSL2 modulate the effector functions of Th17 cells. However, the molecular mechanisms underlying these effects are unclear, owing to the poorly characterized protein interaction networks of FOSL factors. Here, we establish the first interactomes of FOSL1 and FOSL2 in human Th17 cells, using affinity purification-mass spectrometry analysis. In addition to the known JUN proteins, we identified several novel binding partners of FOSL1 and FOSL2. Gene ontology analysis found a significant fraction of these interactors to be associated with RNA-binding activity, which suggests new mechanistic links. Intriguingly, 29 proteins were found to share interactions with FOSL1 and FOSL2, and these included key regulators of Th17 fate. We further validated the binding partners identified in this study by using parallel reaction monitoring targeted mass spectrometry and other methods. Our study provides key insights into the interaction-based signaling mechanisms of FOSL proteins that potentially govern Th17 cell differentiation and associated pathologies.

OriginalspråkEngelska
Sidor (från-till)24834-24847
Antal sidor14
TidskriftACS Omega
Volym6
Utgåva38
DOI
StatusPublicerad - 28 sep. 2021
MoE-publikationstypA1 Tidskriftsartikel-refererad

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