Mechanism of PSMD10 in homocysteine activating hepatocyte autophagy and promoting liver injury / 中国药理学通报

Aim To discuss the mechanism of proteasome 26S subunit non-ATPase 10(PSMD10) activating hepatocyte autophagy and promoting liver injury by in homocysteine. Methods Wild mice and cystathionine β-synthase (CBS) gene knockout mice were used and divided into normal (cbs

Role of a 19S Proteasome Subunit- PSMD10(Gankyrin) in Neurogenesis of Human Neural Progenitor Cells

PSMD10(Gankyrin), a proteasome assembly chaperone, is a widely known oncoprotein which aspects many hall mark properties of cancer. However, except proteasome assembly chaperon function its role in normal cell function remains unknown. To address this issue, we induced PSMD10(Gankyrin) overexpression in HEK293 cells and the resultant large-scale changes in gene expression profile were analyzed. We constituted networks from microarray data of these differentially expressed genes and carried out extensive topological analyses. The overrecurring yet consistent theme that appeared throughout analysis using varied network metrics is that all genes and interactions identified as important would be involved in neurogenesis and neuronal development. Intrigued we tested the possibility that PSMD10(Gankyrin) may be strongly associated with cell fate decisions that commit neural stem cells to differentiate into neurons. Overexpression of PSMD10(Gankyrin) in human neural progenitor cells facilitated neuronal differentiation via β-catenin Ngn1 pathway. Here for the first time we provide preliminary and yet compelling experimental evidence for the involvement of a potential oncoprotein – PSMD10(Gankyrin), in neuronal differentiation.

Expression of PSMD10 and Ki67 in epithelial ovarian carcinoma and its clinicopathological significance / 实用肿瘤学杂志

Objective The objective of this study was to investigate the expression of PSMD10 and Ki67 in epithelial ovarian tumors and its clinicopathological significance.Methods Immunohistochemical method was used to detect the expression of PSMD10 and Ki67 in 21 cases of ovarian benign tumor,31 cases of ovarian borderline tumor and 156 cases of ovarian cancer.Results The positive expression rate of PSMD10 and Ki67 in ovarian cancer was significantly higher than those of ovarian borderline and benign tumor(P0.05).There was significant different the positive expression rate of PSMD10 from clinical stage,pathological grade and residual tumor diameter(P<0.05).There was a positive correlation between the expression of PSMD10 and Ki67 in ovarian cancer(P<0.01).Conclusion PSMD10 and Ki67 play an important synergistic role in the carcinogenesis and progression of epithelial ovarian cancer.It can be used as an important index to judge the degree of malignancy and progression of ovarian cancer.Joint testing PSMD10 and Ki67 are used to guide the clinical diagnosis.

Functional characterization of human oncoprotein gankyrin in Zebrafish

Gankyrin is an oncoprotein containing seven ankyrin repeats that is overexpressed in hepatocellular carcinoma (HCC). Gankyrin binds to Mdm2, which results in accelerated ubiquitylation via degradation of p53, and it also plays an important role in cell proliferation. However, little is known about the relationships between p53 levels, cell proliferation, and gankyrin over-expression. In order to investigate the influence of gankyrin protein on p53 and Mdm2 in a zebrafish model, we injected human gankyrin (hgankyrin) containing expression vectors (pCS2-hgankyrin, pCS2-hgankyrin-EGFP) into zebrafish embryos. To measure p53 and Mdm2 expression in hgankyrin-injected embryos, RT-PCR, Northern blot and in-situ hybridization and BrdU immunostaining were used. In addition, to know the effect of hgankyrin on cell proliferation in vitro, cell viability assays such as MTT, trypan blue staining and RT-PCR following transfection of hgankyrin-containing vector into HEK 293 cell line were performed. In vivo results indicated that p53 mRNA levels decreased but those of Mdm2 were not decreased in the presence of hgankyrin. These results suggest that gankyrin downregulates p53 expression and not Mdm2 expression. In the study of cell proliferation, BrdU-positive cells were predominantly increased in the head and tail regions in hgankyrin-injected zebrafish. Additional in vitro studies using trypan blue staining and MTT assay showed that gankyrin-expressing HEK 293 cells proliferated at a faster rate, indicating that gankyrin promotes cell proliferation. Our results demonstrate that hgankyrin overexpression downregulates p53 expression and promotes cell proliferation in zebrafish. Gankyrin may play an important role in tumorigenesis via its effects on p53 and cell proliferation.