The cleavage of microphthalmia-associated transcription factor, MITF, by caspases plays an essential role in melanocyte and melanoma cell apoptosis
The cleavage of microphthalmia-associated transcription factor, MITF, by caspases plays an essential role in melanocyte and melanoma cell apoptosis
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DOI：
10.1101/gad.335905
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发表时间：
2005-09-01
影响因子：
10.5
通讯作者：
Bertolotto, C
中科院分区：
文献类型：
--
作者：
Larribere, L;Hilmi, C;Bertolotto, C
小眼相关转录因子（MITF） m型是一种黑素细胞特异性转录因子，在黑素细胞的发育、存活和分化中起关键作用。在这里，我们确定了MITF是caspases的一个新的底物，并在c端结构域的Asp 345之后确定了切割位点。我们发现，一种不可切割形式的MITF的表达使黑色素瘤细胞抵抗凋亡刺激，并且我们发现caspase切割产生的c端片段具有促凋亡活性，使黑色素瘤细胞对死亡信号敏感。半胱天冬酶加工MITF后获得的促凋亡功能为调节黑素细胞和黑色素瘤细胞的死亡提供了一种组织限制的手段。
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.