Research ArticleCancer

The E3 ligase APC/CCdh1 promotes ubiquitylation-mediated proteolysis of PAX3 to suppress melanocyte proliferation and melanoma growth

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Science Signaling  01 Sep 2015:
Vol. 8, Issue 392, pp. ra87
DOI: 10.1126/scisignal.aab1995

Sensitizing melanoma to chemotherapeutic drugs

APC/C is an E3 ubiquitin ligase complex that coordinates aspects of the cell cycle by targeting cell cycle regulators, such as cyclins, for destruction. Cao et al. found that Cdh1, a component of this complex, restricted cell proliferation in melanocytes by promoting the degradation of the transcription factor PAX3. However, Cdh1 abundance was decreased in primary and advanced melanoma patient samples compared to normal skin tissue, and the abundance of PAX3 was increased. Restoring Cdh1 abundance in melanoma cells in culture and in xenografts in mice suppressed their proliferation and increased their sensitivity to the chemotherapeutic agent doxorubicin. The findings indicate that inhibition of Cdh1 could enable traditional chemotherapeutic drugs to be effective in melanoma.

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