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bioRxiv · 10.64898/2026.08.01.742203

Oncogenic NPM-ALK reprograms the TGM1 1 interactome toward oncogenic signaling and transcriptional states

Taguchi, S.·Higashi, K.·Tanaka, Y.·Kosako, H.·Aoyama, K.
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Abstract

Oncogenic NPM-ALK drives aberrant signaling networks that promote malignant phenotypes; however, the molecular mechanisms linking oncogenic signaling to downstream cellular programs remain incompletely understood. Among candidate regulatory factors, transglutaminase 1 (TGM1) has not been functionally characterized in this context. Here, we investigated the role of TGM1 in NPM-ALK-expressing cells by combining proximity-dependent proteomics with functional analyses. Using a TurboID- based approach, we mapped the TGM1-associated protein network and identified extensive remodeling of this network upon NPM-ALK expression. Proteomic analyses revealed that NPM-ALK reduced TGM1-associated proteins involved in genome maintenance and DNA repair, while enhancing associations with proteins linked to cytoplasmic translation and PI3K-AKT signaling pathways. Consistent with these findings, TGM1 deficiency impaired cell proliferation without significantly affecting cell viability, indicating a specific role in maximal proliferative capacity. Furthermore, proteomic and functional analyses suggested a link between TGM1 and AKT signaling pathways. Together, these findings suggest that oncogenic NPM-ALK reprograms the TGM1 interactome toward oncogenic signaling and transcriptional states, positioning TGM1 within signaling networks associated with proliferative cellular phenotypes.

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Taguchi, S., Higashi, K., Tanaka, Y., Kosako, H., Aoyama, K.. 2026-08-03. Oncogenic NPM-ALK reprograms the TGM1 1 interactome toward oncogenic signaling and transcriptional states. https://doi.org/10.64898/2026.08.01.742203

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