Ubiquitylation of a melanosomal protein by HECT-E3 ligases serves as sorting signal for lysosomal degradation.
The production of pigment by melanocytic cells of the skin involves a series of enzymatic reactions that take place in specialized organelles called melanosomes. Melan-A/MART-1 is a melanocytic transmembrane protein with no enzymatic activity that accumulates in vesicles at the trans side of the Golgi and in melanosomes. We show ... here that, in melanoma cells, Melan-A associates with two homologous to E6-AP C-terminus (HECT)-E3 ubiquitin ligases, NEDD4 and Itch, and is ubiquitylated. Both NEDD4 and Itch participate in the degradation of Melan-A. A mutant Melan-A lacking ubiquitin-acceptor residues displays increased half-life and, in pigmented cells, accumulates in melanosomes. These results suggest that ubiquitylation regulates the lysosomal sorting and degradation of Melan-A/MART-1 from melanosomes in melanocytic cells.
Mesh Terms:
Antigens, Neoplasm, Cell Line, Endosomal Sorting Complexes Required for Transport, Humans, Lysosomes, Melanosomes, Neoplasm Proteins, Proteasome Endopeptidase Complex, Protein Binding, Repressor Proteins, Ubiquitin, Ubiquitin-Protein Ligases
Antigens, Neoplasm, Cell Line, Endosomal Sorting Complexes Required for Transport, Humans, Lysosomes, Melanosomes, Neoplasm Proteins, Proteasome Endopeptidase Complex, Protein Binding, Repressor Proteins, Ubiquitin, Ubiquitin-Protein Ligases
Mol. Biol. Cell
Date: Apr. 01, 2005
PubMed ID: 15703212
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