| Autor: |
Cedric Messaoudi, Laetitia Besse, Liliana Mirabal-Ortega, Corine Bertolotto, Charlène Estrada, Celio Pouponnot, Florent Dingli, Damarys Loew, Sabine Druillennec, Alain Eychène |
| Rok vydání: |
2021 |
| Předmět: |
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| Popis: |
The MITF transcription factor and the RAS/RAF/MEK/ERK pathway are two interconnected main players in melanoma. Understanding how MITF activity is regulated represents a key question since its dynamic modulation is involved in the phenotypic plasticity of melanoma cells and their resistance to therapy. By investigating the role of ARAF in NRAS-driven melanoma through mass spectrometry experiments followed by a functional siRNA-based screen, we unexpectedly identified MITF as a direct ARAF partner. Interestingly, this interaction is conserved among the RAF protein kinase family since the formation of BRAF/MITF and CRAF/MITF complexes was also observed in the cytosol of NRAS-mutated melanoma cells. The interaction occurs through the kinase domain of RAF proteins and is correlated with their kinase activity level. RAF/MITF complexes modulate MITF nuclear localization by inducing an accumulation of MITF in the cytoplasm, thus negatively controlling its transcriptional activity. Taken together, our study highlights a new level of regulation between two major mediators of melanoma progression, MITF and the MAPK/ERK pathway, which appears more complex than previously anticipated. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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