Anovel ubiquitin ligase, which targets TSLC-1

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In the present study, we explore the pathobiological property of skeletrophin, which targets to Notch ligands and TSLC1. Interestingly, skeletrophin mediated mono-ubiquitination followed by endocytosis of the target surface membrane protein. CM/mina' RING motif of the skeletrophin, also described as mind bomb-2 (mib2), is necessary for monoubiquitination of the substrates. We also identified the promoter region of the skeletrophin gene and found that aberrant hypermethylation is responsible for silencing of skeletrophin expression in malignant melanoma and lung cancer. Monoubiquitination followed by the endocytosis appeared to play an important role of ligands-dependent Notch activation. These resent findings may indicated that aberrant or silencing of skeletrophin expression contribute the tumor development through cancer-stromal interaction.I expect that the present findings may contribute the fundamental understandings of cancer-stromal reaction, further develop the new approach for malignant melanoma and lung cancer.