MITF-M dimer binds the PPARGC1A promoter

Stable Identifier
R-HSA-9854912
Type
Reaction [binding]
Species
Homo sapiens
Compartment
nucleoplasm
ReviewStatus
5/5
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MITF-M dimer binds the PPARGC1A promoter
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MITF-M binds to M-box elements in the promoter of PPARGC1A to drive its expression as assessed by ChIP and reporter gene assay (Vazquez et al, 2013; Haq et al, 2013). Expression of PPARGC1A is low in primary melanocytes but upregulated in the subset of melanomas with high MITF-M expression. Together, MITF-M and PPARGC1A stimulate expression of a panel of genes involved in oxidative phosphorylation and mitochondrial biogenesis. In this way, MITF-M contributes to the metabolic reprogramming of cells downstream of PPARGC1A (Huber et al, 2003; Vazquez et al, 2013; Haq et al, 2103; reviewed in Goding and Arnheiter, 2019).
This signaling axis is also regulated by the MAP kinase pathway: melanoma cells expressing BRAF V600E have lower expression levels of MITF-M and consequently lower expression of PPARGC1A than melanomas with wild-type BRAF, and are more dependent on glycolysis for energy production and other metabolic needs. Inhibition of BRAF in melanoma shifts metabolic programming towards oxidative phosphorylation through an upregulation of MITF-M expression (Haq et al, 2013; reviewed in Goding and Arnheiter, 2019; Falletta et al, 2022)
Literature References
PubMed ID Title Journal Year
35912100 Connecting Metabolic Rewiring With Phenotype Switching in Melanoma

Vivas-García, Y, Goding, CR, Falletta, P

Front Cell Dev Biol 2022
31123060 MITF-the first 25 years

Arnheiter, H, Goding, CR

Genes Dev 2019
12944398 A tissue-restricted cAMP transcriptional response: SOX10 modulates alpha-melanocyte-stimulating hormone-triggered expression of microphthalmia-associated transcription factor in melanocytes

Widlund, HR, Davis, IJ, Wegner, M, Fisher, DE, Price, ER, Huber, WE, Du, J

J Biol Chem 2003
23416000 PGC1α expression defines a subset of human melanoma tumors with increased mitochondrial capacity and resistance to oxidative stress

Widlund, HR, Bhalla, K, Spiegelman, BM, Puigserver, P, Girnun, G, Clish, CB, Lim, JH, Pierce, K, Granter, SR, Chim, H, Vazquez, F

Cancer Cell 2013
23477830 Oncogenic BRAF regulates oxidative metabolism via PGC1α and MITF

Andreu-Perez, P, Nellore, A, Hurley, AD, Song, JS, Edelman, H, Kung, AL, Rowe, GC, Yokoyama, S, Fisher, DE, Arany, Z, Shoag, J, Wargo, JA, Widlund, HR, Frederick, DT, Haq, R

Cancer Cell 2013
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Authored
Rothfels, K  (2023-11-10)
Reviewed
de la Serna, IL  (2024-05-21)
Arnheiter, H  (2024-02-26)
Steingrímsson, E  (2024-11-05)
Vu, HN  (2024-11-05)
Created
Rothfels, K  (2023-11-28)
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