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Neural precursor cell expressed developmentally downregulated 4 (NEDD4), an E3 ubiquitin ligase, is commonly upregulated in human hepatocellular carcinoma (HCC) and functions as an oncogenic factor in the progression of HCC, but the molecular mechanism needs be further explored. In this study, we found that NEDD4 could facilitate the proliferation of HCC cells, which was associated with regulating the ERK signaling. Further investigation showed that protocadherin 17 (PCDH17) was a potential substrate of NEDD4, and restoration of PCDH17 could block the facilitation of ERK signaling and HCC cells proliferation induced by NEDD4 overexpression. Whereafter, we confirmed that NEDD4 interacted with PCDH17 and promoted the Lys33-linked polyubiquitination and degradation of it via the proteasome pathway. Finally, NEDD4 protein level was found to be inversely correlated with that of PCDH17 in human HCC tissues. In conclusion, these results suggest that NEDD4 acts as an E3 ubiquitin ligase for PCDH17 ubiquitination and degradation thereby promoting the proliferation of HCC cells through regulating the ERK signaling, which may provide novel evidence for NEDD4 to be a promising therapeutic target for HCC. [ABSTRACT FROM AUTHOR]

Effects of the trace element germanium (Ge) on the quench sensitivity of an Al-Zn-Mg-Zr alloy were investigated in the present work. The results showed that the Ge-bearing alloy exhibited lower quench sensitivity as compared to the Ge-free alloy. This phenomenon could be reasonably interpreted in terms of the stability of supersaturated solid solution of alloys after quenching from an elevated temperature. The apparent vacancy formation energies for the Ge-free and Ge-bearing alloys were determined to be 0.49 and 0.58 eV respectively. This suggested that the addition of a small amount of Ge was able to trap excess vacancies, leading to a decrease in the amount of coarse dispersoids and resultant low quench sensitivity in Ge-bearing alloys. Therefore, Ge could be used in alloy productions, which require a slow cooling rate to reduce the residual stresses and distortions. [ABSTRACT FROM AUTHOR]