The emerging multifaceted role of PINK1 in cancer biology.

For its various important functions in cells, phosphatase and tensin homolog-induced kinase 1 (PINK1) has drawn considerable attention for the role it plays in early-onset Parkinson's disease. In recent years, emerging evidence has supported the hypothesis that PINK1 plays a part in regulating many physiological and pathophysiological processes in cancer cells, including cytoplasmic homeostasis, cell survival, and cell death. According to the findings of these studies, PINK1 can function as a tumor promoter or suppressor, showing a duality that is dependent on the context. In this study we review the mechanistic characters relating to PINK1 based on available published data from peer-reviewed articles, The Cancer Genome Atlas data mining, and cell-based assays. This mini review focuses on some of the interplays between PINK1 and the context and recent developments in the field, including its growing involvement in mitophagy and its nonmitophagy organelles-related function. This review aims to help readers better grasp how PINK1 is functioning in cell physiological and pathophysiological processes, especially in cancer biology.

[Rescued influenza A virus with codon deoptimized NS1 gene is attenuated both in vitro and in vivo].

Abstract: To develop novel live attenuated influenza vaccine, we explored the feasibility to attenuate influenza virus by codon deoptimization of NS1. According to the codon usage bias in influenza A virus, we designed and synthesized a condon-deoptimized NS gene by substituting codons of 110 amino acids in the NS1 gene of A/Puerto Rico/8/34(H1N1) with unpreferred synonymous codons. The influenza A virus with the codon deoptimized NS1 gene (deoNS virus) was rescued by reverse genetics. Plaque forming assay and virus growth curve showed that the growth of deoNS virus was reduced about 1000 times in MDCK cells compared to that of the wild-type virus. Intranasal inoculation with deoNS virus did not cause death or evident disease in infected BALB/c mice. Furthermore, the virus titer in the lungs of mice infected with deoNS virus was significantly lower (i.e. 100-1000 times) than that of wild-type virus. Our results indicated that influenza virus could be effectively attenuated by synonymous codon deoptimization of NS1 gene. This strategy will be useful to develop new attenuated candidates for the production of live attenuated influenza vaccines.