The cleavage of microphthalmia-associated transcription factor, MITF, by caspases plays an essential role in melanocyte and melanoma cell apoptosis (original) (raw)

  1. Lionel Larribere1,
  2. Caroline Hilmi1,
  3. Mehdi Khaled1,
  4. Cédric Gaggioli1,
  5. Karine Bille1,
  6. Patrick Auberger2,
  7. Jean Paul Ortonne1,
  8. Robert Ballotti1, and
  9. Corine Bertolotto1,3
  10. 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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