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Siah1/2 Ubiquitin Ligases in ER Stress Signaling in Melanoma

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Technical Report,30 Sep 2014,29 Sep 2015

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Sanford-Burnham Medical Research Institute La Jolla United States

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The task of identifying novel and significant ER stress related changes that are regulated by ubiquitin ligases was initiated with a focus on Siah12, which led to a distinct understanding of these ligases impact on melanoma, a study which continues. We have also identified the ubiquitin ligase RNF5, as one that regulates the immune checkpoint control mechanism, an ER stress associated ligase. We continue with exciting and significant studies as we define unexpected ER-stress related roles for the ubiquitin ligase RNF5 in melanoma. Lastly, our unbiased search for ubiquitin ligases that may affect melanoma resistance to BRAF inhibitor therapy led us to identify and characterize RNF125, which is downregulated in resistant tumors with concomitant increase in JAK1 and receptor tyrosine kinases. These important findings were published in Cell Reports 2015 and pave a path for new clinical trial for patients with resistant melanoma to BRAF inhibitors. We expect that the work with our current subset of Siah12 inhibitors will be summarized for publication during 20167.


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