lauren-langbein

[lauren-langbein]

Slide presentation

Please click the link below to view my presentation, entitled “Connections between BAP1 and the type I interferon pathway in clear cell kidney cancer.”

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https://www.slideshare.net/secret/35zcP4K8IYjVWd

[lauren-langbein]

Abstract

Connections between BAP1 and the Type I Interferon Pathway in clear cell kidney cancer

BRCA1-associated protein 1 (BAP1) is a deubiquitinase that is mutated in 10-15% of clear cell renal cell carcinoma (ccRCC). Despite the association between BAP1 loss and aggressive disease, the specific role of BAP1 in disease development and/or progression remains unclear. In this study, we found that BAP1 regulates the expression of STAT2 and IRF9, components of the interferon stimulated gene factor 3 (ISGF3) transcription factor involved in Type I interferon signaling. BAP1 enhances ISGF3 levels and downstream target expression, which depends on its deubiquitinase activity, and promotes IFN-β expression. Suppression of IFNAR1 or inhibition of JAK1 abrogates the effect of BAP1 on ISGF3, suggesting that autocrine IFN signaling through the interferon α/β receptor is necessary for this pathway. Additionally, our xenograft mouse models suggest BAP1 indeed functions as a tumor suppressor in ccRCC. Together, our results indicate that BAP1 loss in ccRCC reduces ISGF3 function, which may influence several aspects of ccRCC tumor biology.