Titill: | MITF has a central role in regulating starvation-induced autophagy in melanoma |
Höfundur: |
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Útgáfa: | 2019-01-31 |
Tungumál: | Enska |
Umfang: | 1055 |
Háskóli/Stofnun: | Háskóli Íslands University of Iceland |
Svið: | Heilbrigðisvísindasvið (HÍ) School of Health Sciences (UI) |
Deild: | Læknadeild (HÍ) Faculty of Medicine (UI) Lífvísindasetur (HÍ) Biomedical Center (UI) |
Birtist í: | Scientific Reports;9(1) |
ISSN: | 2045-2322 |
DOI: | 10.1038/s41598-018-37522-6 |
Efnisorð: | Macroautophagy; Melanoma; Genarannsóknir; Húðkrabbamein |
URI: | https://hdl.handle.net/20.500.11815/1577 |
Tilvitnun:Möller, K., Sigurbjornsdottir, S., Arnthorsson, A.O. et al. MITF has a central role in regulating starvation-induced autophagy in melanoma. Sci Rep 9, 1055 (2019). https://doi.org/10.1038/s41598-018-37522-6
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Útdráttur:The MITF transcription factor is a master regulator of melanocyte development and a critical factor in
melanomagenesis. The related transcription factors TFEB and TFE3 regulate lysosomal activity and
autophagy processes known to be important in melanoma. Here we show that MITF binds the CLEARbox element in the promoters of lysosomal and autophagosomal genes in melanocytes and melanoma
cells. The crystal structure of MITF bound to the CLEAR-box reveals how the palindromic nature of this
motif induces symmetric MITF homodimer binding. In metastatic melanoma tumors and cell lines, MITF
positively correlates with the expression of lysosomal and autophagosomal genes, which, interestingly,
are diferent from the lysosomal and autophagosomal genes correlated with TFEB and TFE3. Depletion
of MITF in melanoma cells and melanocytes attenuates the response to starvation-induced autophagy,
whereas the overexpression of MITF in melanoma cells increases the number of autophagosomes but
is not sufcient to induce autophagic fux. Our results suggest that MITF and the related factors TFEB
and TFE3 have separate roles in regulating a starvation-induced autophagy response in melanoma.
Understanding the normal and pathophysiological roles of MITF and related transcription factors may
provide important clinical insights into melanoma therapy.
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Athugasemdir:Publisher's version (útgefin grein).
Supplementary information accompanies this paper at https://doi.org/10.1038/s41598-018-37522-6.
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Leyfi:Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
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