IKK2/β mediated phosphorylation of transcription factor Ets2 at site(s) distal to DNA binding domain negatively modulates its DNA binding activity
- 1Bose Institute
Abstract
Transcription factor Ets2 coalesce with the NF-{kappa}B pathway to regulate gene expression in specific signaling contexts. IKK2/{beta}-mediated phosphorylation events critically regulate the NF-{kappa}B pathway. However, any link between Ets2 and IKK2 remains elusive. Here we report Ets2 as a direct substrate of IKK2. In-vitro kinase assays using deletion constructs, high resolution MS-MS and site directed mutagenesis identified S295 as a prominent phosphorylation site distal to the DNA binding domain, substitution of which to phosphor-mimetic Glutamate triggers further phosphorylation of Ets2. MD simulations clearly indicate conformational constriction of the otherwise disordered N-terminal region and inhibition of DNA binding activity upon phosphorylation, which was further confirmed by Electrophoretic mobility shift assays. Our results uncover a phosphoregulatory connection between Ets2 and IKK2.
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BibTeX
@misc{sutradhar2026ikk2β,
title = {{IKK2/β mediated phosphorylation of transcription factor Ets2 at site(s) distal to DNA binding domain negatively modulates its DNA binding activity}},
author = {D. Sutradhar and A. R. Antony and A. Haque and P. Borar and P. T. Rao and S. Raychaudhuri and P. Kumar and S. Polley},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.31.747788},
url = {https://www.biorxiv.org/content/10.64898/2026.08.31.747788v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - IKK2/β mediated phosphorylation of transcription factor Ets2 at site(s) distal to DNA binding domain negatively modulates its DNA binding activity
AU - D. Sutradhar
AU - A. R. Antony
AU - A. Haque
AU - P. Borar
AU - P. T. Rao
AU - S. Raychaudhuri
AU - P. Kumar
AU - S. Polley
PY - 2026
DA - 2026/08/31
PB - bioRxiv
DO - 10.64898/2026.08.31.747788
UR - https://www.biorxiv.org/content/10.64898/2026.08.31.747788v1
AB - Transcription factor Ets2 coalesce with the NF-{kappa}B pathway to regulate gene expression in specific signaling contexts. IKK2/{beta}-mediated phosphorylation events critically regulate the NF-{kappa}B pathway. However, any link between Ets2 and IKK2 remains elusive. Here we report Ets2 as a direct substrate of IKK2. In-vitro kinase assays using deletion constructs, high resolution MS-MS and site directed mutagenesis identified S295 as a prominent phosphorylation site distal to the DNA binding domain, substitution of which to phosphor-mimetic Glutamate triggers further phosphorylation of Ets2. MD simulations clearly indicate conformational constriction of the otherwise disordered N-terminal region and inhibition of DNA binding activity upon phosphorylation, which was further confirmed by Electrophoretic mobility shift assays. Our results uncover a phosphoregulatory connection between Ets2 and IKK2.
ER -