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KMID : 0624620110440040267
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BMB Reports
2011 Volume.44 No. 4 p.267 ~ p.272
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ZAS3 promotes TNFα-induced apoptosis by blocking NFκB-activated expression of the anti-apoptotic genes TRAF1 and TRAF2
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Shin Dong-Hyeon
Park Kye-Won
Wu Lai-Chu
Hong Joung-Woo
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Abstract
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ZAS3 is a large zinc finger transcription repressor that binds the ?B-motif via two signature domains of ZASN and ZASC. A loss-of-function study showed that lack of ZAS3 protein induced accelerated cell proliferation and tumorigenesis. Conversely, gain-of-function studies showed that ZAS3 repressed NF?B-activated transcription by competing with NF?B for the ?B-motif. Based on these observations, we hypothesize that ZAS3 promotes apoptosis by interrupting anti-apoptotic activity of NF?B. Here, we present evidence that upon TNFα stimulation, ZAS3 inhibits NF?B-mediated cell survival and promotes caspase-mediated apoptosis. The inhibitory effect of ZAS3 on NF?B activity is mediated by neither direct association with NF?B nor disrupting nuclear localization of NF?B. Instead, ZAS3 repressed the expression of two key anti-apoptotic genes of NF?B, TRAF1 and TRAF2, thereby sensitizing cells to TNFα-induced cell death. Taken together, our data suggest that ZAS3 is a tumor suppressor gene and therefore serves as a novel therapeutic target for developing anti-cancer drugs.
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KEYWORD
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Anti-apoptosis, NFκB, TNFα signaling, Tumor suppression, ZAS3
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