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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Apoptosis / physiology*
-
Base Sequence
-
Binding Sites / genetics
-
Caspases / metabolism*
-
Cell Line, Tumor
-
Cells, Cultured
-
DNA-Binding Proteins / chemistry
-
DNA-Binding Proteins / genetics
-
DNA-Binding Proteins / metabolism*
-
Humans
-
Melanocytes / cytology*
-
Melanocytes / metabolism*
-
Melanoma / metabolism*
-
Melanoma / pathology*
-
Melanoma, Experimental / metabolism
-
Melanoma, Experimental / pathology
-
Mice
-
Microphthalmia-Associated Transcription Factor
-
Protein Processing, Post-Translational
-
Protein Structure, Tertiary
-
RNA, Small Interfering / genetics
-
Substrate Specificity
-
Transcription Factors / chemistry
-
Transcription Factors / genetics
-
Transcription Factors / metabolism*
Substances
-
DNA-Binding Proteins
-
MITF protein, human
-
Microphthalmia-Associated Transcription Factor
-
Mitf protein, mouse
-
RNA, Small Interfering
-
Transcription Factors
-
Caspases