Cytoplasmic Expression of TP53INP2 Modulated by Demethylase FTO and Mutant NPM1 Promotes Autophagy in Leukemia Cells

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2023 Jan 21

PMID 36675134

Authors

Junpeng Huang

Minghui Sun

Yonghong Tao

Jun Ren

Meixi Peng

Yipei Jing

Qiaoling Xiao

Jing Yang

Can Lin

Li Lei

Zailin Yang

Ling Zhang

Affiliations

Soon will be listed here.

Abstract

Acute myeloid leukemia (AML) with a () mutation is a unique subtype of adult leukemia. Recent studies show that -mutated AML has high autophagy activity. However, the mechanism for upholding the high autophagic level is still not fully elucidated. In this study, we first identified that tumor protein p53 inducible nuclear protein 2 (TP53INP2) was highly expressed and cytoplasmically localized in -mutated AML cells. Subsequent data showed that the expression of TP53INP2 was upregulated by fat mass and obesity-associated protein (FTO)-mediated mA modification. Meanwhile, TP53INP2 was delocalized to the cytoplasm by interacting with NPM1 mutants. Functionally, cytoplasmic TP53INP2 enhanced autophagy activity by promoting the interaction of microtubule-associated protein 1 light chain 3 (LC3) - autophagy-related 7 (ATG7) and further facilitated the survival of leukemia cells. Taken together, our study indicates that TP53INP2 plays an oncogenic role in maintaining the high autophagy activity of -mutated AML and provides further insight into autophagy-targeted therapy of this leukemia subtype.

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