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N6-methyladenosine-modified USP13 induces pro-survival autophagy and imatinib resistance via regulating the stabilization of autophagy-related protein 5 in gastrointestinal stromal tumors by Zhishuang Gao; Chao Li; Haoyu Sun; Yibo Bian; Zhiwei Cui; Nuofan Wang; Zhangjie Wang; Yang Yang; Zonghang Liu; Zhongyuan He; Bowen Li; Fengyuan Li; Zheng Li; Linjun Wang; Diancai Zhang; Li Yang; Zekuan Xu; Xueming Li; Hao Xu is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is N6-methyladenosine-modified USP13 induces pro-survival autophagy and imatinib resistance via regulating the stabilization of autophagy-related protein 5 in gastrointestinal stromal tumors about?

Secondary resistance to imatinib (IM) represents a major challenge for therapy of gastrointestinal stromal tumors (GISTs). Aberrations in oncogenic pathways, including autophagy, correlate with IM resistance. Regulation of autophagy-related protein 5 (ATG5) by the ubiquitin-proteasome system is critical for autophagic activity, although the molecular mechanisms that underpin reversible deubiquitination of ATG5 have not been deciphered fully. Here, we identified USP13 as an essential deubiquitinase that stabilizes ATG5 in a process that depends on the PAK1 serine/threonine-protein kinase and which enhances autophagy and promotes IM resistance in GIST cells. USP13 preferentially is induced in GIST cells by IM and interacts with ATG5, which leads to stabilization of ATG5 through deubiquitination. Activation of PAK1 promoted phosphorylation of ATG5 thereby enhancing the interaction of ATG5 with USP13. Furthermore, N 6 -methyladenosine methyltransferase-like 3 (METTL3) mediated stabilization of USP13 mRNA that required the m 6 A reader IGF2BP2. Moreover, an inhibitor of USP13 caused ATG5 decay and co-administration of this inhibitor with 3-methyladenine boosted treatment efficacy of IM

Who reads N6-methyladenosine-modified USP13 induces pro-survival autophagy and imatinib resistance via regulating the stabilization of autophagy-related protein 5 in gastrointestinal stromal tumors?

Author

Zhishuang Gao; Chao Li; Haoyu Sun; Yibo Bian; Zhiwei Cui; Nuofan Wang; Zhangjie Wang; Yang Yang; Zonghang Liu; Zhongyuan He; Bowen Li; Fengyuan Li; Zheng Li; Linjun Wang; Diancai Zhang; Li Yang; Zekuan Xu; Xueming Li; Hao Xu

Publisher

Springer Science and Business Media LLC

Published

2022

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)