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Updated: Jan 7, 2026

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence

Published on: January 7, 2019

USP8-EIF2S1シグナル伝達はTKI誘発ストレス下でのCML細胞生存を増強する

Chethampadi Gopi Mohan¹, Keechilat Pavithran²

¹Amrita School of Nanosciences and Molecular Medicine, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India.

The FEBS journal

|December 26, 2025

Abstract:

CML is primarily driven by the oncogenic BCR-ABL fusion kinase; however, tyrosine kinase inhibitor (TKI) resistance remains a significant clinical challenge. A study by Zang et al. identified USP8 as a critical mediator of this resistance. USP8, a deubiquitinase, stabilizes the stress-response regulator EIF2S1 (eIF2α) by removing K48-linked ubiquitin chains. This stabilization sustains PERK-EIF2S1-mediated unfolded protein response (UPR) signaling. The UPR suppresses general protein translation while promoting the expression of adaptive stress-response genes, allowing CML cells to survive TKI-induced stress. Consequently, targeting the USP8-EIF2S1 axis is proposed as a key therapeutic strategy to overcome resistance and enhance patient outcomes.

キーワード:

TKI耐性薬 UPRシグナル伝達慢性骨髄性白血病脱ユビキチン化酵素構造ベース創薬ユビキチン特異的プロテアーゼファミリー

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