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Tabughang Franklin Chi, Fawzi Khoder-Agha, Daniela Mennerich, Sakari Kellokumpu, IIkka Miinalainen, Thomas Kietzmann, Elitsa Y. Dimova, Loss of USF2 promotes proliferation, migration and mitophagy in a redox-dependent manner, Redox Biology, Volume 37, 2020, 101750, ISSN 2213-2317, https://doi.org/10.1016/j.redox.2020.101750

Loss of USF2 promotes proliferation, migration and mitophagy in a redox-dependent manner

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Author: Chi, Tabughang Franklin1; Khoder-Agha, Fawzi1; Mennerich, Daniela1;
Organizations: 1Faculty of Biochemistry and Molecular Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 5.6 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe202102033592
Language: English
Published: Elsevier, 2020
Publish Date: 2021-02-03
Description:

Abstract

The upstream stimulatory factor 2 (USF2) is a transcription factor implicated in several cellular processes and among them, tumor development seems to stand out. However, the data with respect to the role of USF2 in tumor development are conflicting suggesting that it acts either as tumor promoter or suppressor. Here we show that absence of USF2 promotes proliferation and migration. Thereby, we reveal a previously unknown function of USF2 in mitochondrial homeostasis. Mechanistically, we demonstrate that deficiency of USF2 promotes survival by inducing mitophagy in a ROS-sensitive manner by activating both ERK1/2 and AKT.

Altogether, this study supports USF2′s function as tumor suppressor and highlights its novel role for mitochondrial function and energy homeostasis thereby linking USF2 to conditions such as insulin resistance, type-2 diabetes mellitus, and the metabolic syndrome.

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Series: Redox biology
ISSN: 2213-2317
ISSN-E: 2213-2317
ISSN-L: 2213-2317
Volume: 37
Article number: 101750
DOI: 10.1016/j.redox.2020.101750
OADOI: https://oadoi.org/10.1016/j.redox.2020.101750
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
Subjects:
Compromised mitochondria
Migration
Mitophagy
Proliferation
Upstream stimulatory factor 2 (USF2)
Article
Funding: This work was supported by the Academy of Finland SA296027, the Jane and Aatos Erkko Foundation, the Finnish Cancer Foundation, the Sigrid Juselius Foundation, the University of Oulu, and Biocenter Oulu.
Academy of Finland Grant Number: 296027
Detailed Information: 296027 (Academy of Finland Funding decision)
Copyright information: © 2020 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license.
  https://creativecommons.org/licenses/by-nc-nd/4.0/