MITF and TFEB cross-regulation in melanoma cells.

PLoS One

Department of Biochemistry and Molecular Biology, Faculty of Medicine, BioMedical Center, University of Iceland, Reykjavík, Iceland.

Published: October 2020

AI Article Synopsis

  • MITF, TFEB, TFE3, and TFEC are transcription factors involved in cellular processes like melanocyte development and lysosome function, with MITF being significant in melanoma.
  • The study reveals that MITF and TFEB, but not TFE3, directly influence each other's gene expression in melanoma cells.
  • Their relationship is regulated by the mTOR signaling pathway, highlighting the complexity of their interactions in regulating important cellular pathways.

Article Abstract

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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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470386PMC
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238546PLOS

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