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Fig. 2 | Cancers of the Head & Neck

Fig. 2

From: The cylindromatosis (CYLD) gene and head and neck tumorigenesis

Fig. 2

CYLD-associated signaling pathways. NF-kB, Wnt/β-catenin, and JNK pathways have been shown to be regulated by CYLD. The canonical NF-kB signaling pathway has been shown to be regulated by CYLD through deubiquitination of target substrates such as RIP1, the TAK1 complex and NEMO [2]. In the non-canonical NF-kB signaling pathway, deubiquitination of Bcl-3 by CYLD results in the inhibition of cyclin D1 gene expression [29]. Wnt/β-catenin signaling has been shown to be regulated by CYLD, via deubiquitination of the (disheveled) DVL protein [6]. The JNK signaling pathway has been demonstrated to be regulated by CYLD activity through unknown mechanisms likely involving TRAF2 and MKK7 [7]. In addition, the Notch/Hes1 pathway and the Hedgehog signaling have been shown to regulate transcription of CYLD, via suppression of CYLD transcription by Hes1 and snail1, respectively [69, 70]. Blue arrows indicate nuclear translocation of the proteins. The lower grey box shows the published signaling changes and likely consequences of CYLD deficiencies due to CYLD knockout, CYLD silencing by siRNA or shRNA or CYLD mutation. Red arrows indicate that the nuclear translocation of the indicated proteins was found to be increased. Potential therapeutic targets due to CYLD aberrations are highlighted in red within the lower grey box

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