Opin vísindi

MITF and TFEB cross-regulation in melanoma cells

MITF and TFEB cross-regulation in melanoma cells

Title: MITF and TFEB cross-regulation in melanoma cells
Author: Ballesteros Alvarez, Josue   orcid.org/0000-0002-9828-9812
Dilshat, Ramile
Fock, Valerie   orcid.org/0000-0002-7812-4340
Möller, Katrin   orcid.org/0000-0002-4720-8568
Karl, Ludwig
LARUE, Lionel   orcid.org/0000-0002-2010-6107
Ogmundsdottir, Margret H
Steingrimsson, Eirikur   orcid.org/0000-0001-5826-7486
Date: 2020-09-03
Language: English
Scope: e0238546
University/Institute: Háskóli Íslands
University of Iceland
School: Heilbrigðisvísindasvið (HÍ)
School of Health Sciences (UI)
Department: Læknadeild (HÍ)
Faculty of Medicine (UI)
Lífvísindasetur (HÍ)
Biomedical Center (UI)
Series: PLOS ONE;15(9)
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0238546
Subject: MITF; TFEB; Melanoma cells; Erfðarannsóknir; Genarannsóknir
URI: https://hdl.handle.net/20.500.11815/2210

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Citation: Ballesteros-Álvarez J, Dilshat R, Fock V, Möller K, Karl L, Larue L, et al. (2020) MITF and TFEB cross-regulation in melanoma cells. PLoS ONE 15(9): e0238546. https://doi.org/10.1371/journal.pone.0238546


The MITF, TFEB, TFE3 and TFEC (MiT-TFE) proteins belong to the basic helix-loop-helix family of leucine zipper transcription factors. MITF is crucial for melanocyte development and differentiation, and has been termed a lineage-specific oncogene in melanoma. The three related proteins MITF, TFEB and TFE3 have been shown to be involved in the biogenesis and function of lysosomes and autophagosomes, regulating cellular clearance pathways. Here we investigated the cross-regulatory relationship of MITF and TFEB in melanoma cells. Like MITF, the TFEB and TFE3 genes are expressed in melanoma cells as well as in melanoma tumors, albeit at lower levels. We show that the MITF and TFEB proteins, but not TFE3, directly affect each other’s mRNA and protein expression. In addition, the subcellular localization of MITF and TFEB is subject to regulation by the mTOR signaling pathway, which impacts their cross-regulatory relationship at the transcriptional level. Our work shows that the relationship between MITF and TFEB is multifaceted and that the cross-regulatory interactions of these factors need to be taken into account when considering pathways regulated by these proteins.


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