MITF and TFEB cross-regulation in melanoma cells
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...
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| Veröffentlicht in: | PloS one 2020-09, Vol.15 (9), p.e0238546-e0238546 |
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| creator | Ballesteros-Álvarez, Josué Dilshat, Ramile Fock, Valerie Möller, Katrín Karl, Ludwig Larue, Lionel Ögmundsdóttir, Margrét Helga Steingrímsson, Eiríkur |
| description | 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. |
| doi_str_mv | 10.1371/journal.pone.0238546 |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0238546</identifier><identifier>PMID: 32881934</identifier><language>eng</language><publisher>San Francisco: Public Library of Science</publisher><subject>Autophagy ; Binding sites ; Biochemistry ; Biology and life sciences ; Deoxyribonucleic acid ; DNA ; Gene expression ; Helix-loop-helix proteins ; Helix-loop-helix proteins (basic) ; Kinases ; Leucine ; Leucine zipper proteins ; Localization ; Lysosomes ; Medicine ; Melanoma ; Microphthalmia-associated transcription factor ; Molecular biology ; Mutation ; Phagosomes ; Proteins ; Research and Analysis Methods ; Signal transduction ; TOR protein ; Transcription factors ; Tumors</subject><ispartof>PloS one, 2020-09, Vol.15 (9), p.e0238546-e0238546</ispartof><rights>2020 Ballesteros-Álvarez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 Ballesteros-Álvarez et al 2020 Ballesteros-Álvarez et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c503t-7b71269f05c502b559458d689e41c7622da91626f81469f699922ecc0f7cb7cc3</citedby><cites>FETCH-LOGICAL-c503t-7b71269f05c502b559458d689e41c7622da91626f81469f699922ecc0f7cb7cc3</cites><orcidid>0000-0002-9828-9812 ; 0000-0002-4720-8568 ; 0000-0001-5826-7486 ; 0000-0002-2010-6107</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470386/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470386/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,2096,2915,23847,27905,27906,53772,53774,79349,79350</link.rule.ids></links><search><contributor>Roemer, Klaus</contributor><creatorcontrib>Ballesteros-Álvarez, Josué</creatorcontrib><creatorcontrib>Dilshat, Ramile</creatorcontrib><creatorcontrib>Fock, Valerie</creatorcontrib><creatorcontrib>Möller, Katrín</creatorcontrib><creatorcontrib>Karl, Ludwig</creatorcontrib><creatorcontrib>Larue, Lionel</creatorcontrib><creatorcontrib>Ögmundsdóttir, Margrét Helga</creatorcontrib><creatorcontrib>Steingrímsson, Eiríkur</creatorcontrib><title>MITF and TFEB cross-regulation in melanoma cells</title><title>PloS one</title><description>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.</description><subject>Autophagy</subject><subject>Binding sites</subject><subject>Biochemistry</subject><subject>Biology and life sciences</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Gene expression</subject><subject>Helix-loop-helix proteins</subject><subject>Helix-loop-helix proteins (basic)</subject><subject>Kinases</subject><subject>Leucine</subject><subject>Leucine zipper proteins</subject><subject>Localization</subject><subject>Lysosomes</subject><subject>Medicine</subject><subject>Melanoma</subject><subject>Microphthalmia-associated transcription factor</subject><subject>Molecular biology</subject><subject>Mutation</subject><subject>Phagosomes</subject><subject>Proteins</subject><subject>Research and Analysis 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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.</abstract><cop>San Francisco</cop><pub>Public Library of Science</pub><pmid>32881934</pmid><doi>10.1371/journal.pone.0238546</doi><orcidid>https://orcid.org/0000-0002-9828-9812</orcidid><orcidid>https://orcid.org/0000-0002-4720-8568</orcidid><orcidid>https://orcid.org/0000-0001-5826-7486</orcidid><orcidid>https://orcid.org/0000-0002-2010-6107</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Autophagy Binding sites Biochemistry Biology and life sciences Deoxyribonucleic acid DNA Gene expression Helix-loop-helix proteins Helix-loop-helix proteins (basic) Kinases Leucine Leucine zipper proteins Localization Lysosomes Medicine Melanoma Microphthalmia-associated transcription factor Molecular biology Mutation Phagosomes Proteins Research and Analysis Methods Signal transduction TOR protein Transcription factors Tumors |
| title | MITF and TFEB cross-regulation in melanoma cells |
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