The cleavage of microphthalmia-associated transcription factor, MITF, by caspases plays an essential role in melanocyte and melanoma cell apoptosis
- Lionel Larribere1,
- Caroline Hilmi1,
- Mehdi Khaled1,
- Cédric Gaggioli1,
- Karine Bille1,
- Patrick Auberger2,
- Jean Paul Ortonne1,
- Robert Ballotti1, and
- Corine Bertolotto1,3
- 1INSERM U597, Biologie et Pathologie des cellules mélanocytaires: de la pigmentation cutanée aux mélanomes, Ligue Nationale contre le Cancer, Equipe labellisée 2001, 06107 NICE Cedex 2, France; 2INSERM U526, Physiopathologie de la mort et la survie cellulaires, Ligue Nationale contre le Cancer, Equipe labellisée 2003, 06107 NICE Cedex 2, France
Abstract
Microphthalmia-associated transcription factor (MITF) M-form is a melanocyte-specific transcription factor that plays a key role in melanocyte development, survival, and differentiation. Here, we identified MITF as a new substrate of caspases and we characterized the cleavage site after Asp 345 in the C-terminal domain. We show that expression of a noncleavable form of MITF renders melanoma cells resistant to apoptotic stimuli, and we found that the C-terminal fragment generated upon caspase cleavage is endowed with a proapoptotic activity that sensitizes melanoma cells to death signals. The proapoptotic function gained by MITF following its processing by caspases provides a tissue-restricted means to modulate death in melanocyte and melanoma cells.
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Footnotes
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Supplemental material is available at http://www.genesdev.org.
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Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.335905.
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↵3 Corresponding author.
↵3 E-MAIL bertolot{at}unice.fr; FAX 33-4-93-81-14-04.
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- Accepted June 28, 2005.
- Received December 24, 2004.
- Cold Spring Harbor Laboratory Press
