MITF and TFEB cross-regulation in melanoma cells

Publisher's version (útgefin grein) 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....

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Bibliographic Details
Published in:PLOS ONE
Main Authors: Ballesteros Alvarez, Josue, Dilshat, Ramile, Fock, Valerie, Möller, Katrin, Karl, Ludwig, LARUE, Lionel, Ogmundsdottir, Margret H, Steingrimsson, Eirikur
Other Authors: Læknadeild (HÍ), Faculty of Medicine (UI), Lífvísindasetur (HÍ), Biomedical Center (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland
Format: Article in Journal/Newspaper
Language:English
Published: Public Library of Science (PLoS) 2020
Subjects:
MITF
TFEB
Melanoma cells
Erfðarannsóknir
Genarannsóknir
Iceland
Online Access:https://hdl.handle.net/20.500.11815/2210
https://doi.org/10.1371/journal.pone.0238546
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Summary:Publisher's version (útgefin grein) 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. ES, 130230-052, Research fund of Iceland, www.rannis.is ES, 163413-051, Research fund of Iceland, www.rannis.is. Peer Reviewed

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