This paper presents the impact of income inequality on the subjective wellbeing of three different social groups in urban China. We classify urban social groups according to their hukou status: rural migrants, "born" urban residents, and "acquired" urban residents who had changed their hukou identity from rural to urban. We focus on how the income disparity between migrants and urban residents affects individual happiness. The main results are as follows. People feel unhappy if inequality is related to their hukou identity, irrespective of whether they are urban residents with or without hukou. However, when identity-related inequality and other individual-and city-level characteristics are controlled, inequality measured by city-level Gini increases happiness. We also find that among urban residents who own hukou, mostly the "acquired" urban residents are unhappy with hukou-related inequality. This implies that identity is formed by both policy and personal experience. "Born" urban residents have lower happiness scores when they are old. Communist Party members strongly dislike the identity-related inequality.

Activation of b-catenin, the central effector of the canonical wingless-type (Wnt) pathway, has been implicated in hepatocellular carcinoma (HCC). However, the transcription regulation mechanism of the b-catenin gene in HCC remains unknown. Here we report that human zinc finger protein 191 (ZNF191) is a potential regulator of b-catenin transcription. ZNF191, a Krüppel-like protein, specifically interacts with the TCAT motif, which constitutes the HUMTH01 microsatellite in the tyrosine hydroxylase (TH) gene ex vivo. We demonstrate that ZNF191 is significantly overexpressed in human HCC specimens and is associated with growth of human HCC cells. Global profiling of gene expression in ZNF191 knockdown human hepatic L02 cells revealed that the important Wnt signal pathway genes b-catenin and cyclin D1 messenger RNAs (mRNAs) are significantly downregulated. In agreement with transcription level, b-catenin and cyclin D1 proteins are also down-regulated in transient and stable ZNF191 knockdown L02 and hepatoma Hep3B cell lines. Moreover, significant correlation between ZNF191 and b-catenin mRNA expression was detected in human HCCs. Promoter luciferase assay indicated that ZNF191 can increase transcription activity of the full-length b-catenin (CTNNB1) promoter, and nucleotide (nt)-1407/-907 of the CTNNB1 promoter exhibited the maximum transcriptional activity. Electrophoretic mobility shift assay showed that purified ZNF191 protein can directly bind to the CTNNB1 promoter, and the binding region is located at nt-1254/-1224. Finally, we demonstrate that the key binding sequence of ZNF191 in vivo is ATTAATT. Conclusion: ZNF191 can directly bind to the CTNNB1 promoter and activate the expression of b-catenin and its downstream target genes such as cyclin D1 in hepatoma cell lines. This study uncovers a new molecular mechanism of transcription regulation of the b-catenin gene in HCC.

Human carbonyl reductase 1 (CBR1) converts the antitumor drug and anthracycline daunorubicin (DNR) into the alcohol metabolite daunorubicinol (DNROL) with significantly reduced antitumor activity and cardiotoxicity, and this limits the clinical use of DNR. Inhibition of CBR1 can thus increase the efficacy and decrease the toxicity of DNR. Here we report that (2)-epigallocatechin gallate (EGCG) from green tea is a promising inhibitor of CBR1. EGCG directly interacts with CBR1 and acts as a noncompetitive inhibitor with respect to the cofactor reduced nicotinamide adenine dinucleotide phosphate and the substrate isatin. The inhibition is dependent on the pH, and the gallate moiety of EGCG is required for activity. Molecular modeling has revealed that EGCG occupies the active site of CBR1. Furthermore, EGCG specifically enhanced the antitumor activity of DNR against hepatocellular carcinoma SMMC7721 cells expressing high levels of CBR1 and corresponding xenografts. We also demonstrated that EGCG could overcome the resistance to DNR by Hep3B cells stably expressing CBR1 but not by RNA interference of CBR1-HepG2 cells. The level of the metabolite DNROL was negatively correlated with that of EGCG in the cell extracts. Finally, EGCG decreased the cardiotoxicity of DNR in a human carcinoma xenograft model with both SMMC7721 and Hep3B cells in mice. Conclusion: These results strongly suggest that EGCG can inhibit CBR1 activity and enhance the effectiveness and decrease the cardiotoxicity of the anticancer drug DNR. These findings also indicate that a combination of EGCG and DNR might represent a novel approach for hepatocellular carcinoma therapy or chemoprevention. (HEPATOLOGY 2010;52:703-714) H epatocellular carcinoma (HCC) is one of the most common malignancies worldwide.

TM accession number AB030189) from mouse brain encoding a homologue of the yeast CWH8 gene is now shown to complement the defects in growth and protein N-glycosylation, and to correct the accumulation of Dol-P-P in the cwh8⌬ yeast mutant. Northern blot analyses demonstrate a wide distribution of the DOLPP1 mRNA in mouse tissues. Overexpression of Dolpp1p in yeast, COS, and Sf9 cells produces substantial increases in Dol-P-P phosphatase activity but not in dolichyl monophosphate or phosphatidic acid phosphatase activities in microsomal fractions. Subcellular fractionation and immunofluorescence studies localize the enzyme encoded by DOLPP1 to the endoplasmic reticulum of COS cells. The results of protease sensitivity studies with microsomal vesicles from the lpp1⌬/dpp1⌬ yeast mutant expressing DOLPP1 are consistent with Dolpp1p having a luminally oriented active site. The sequence of the DOLPP1 cDNA predicts a polypeptide with 238 amino acids, and a new polypeptide corresponding to 27 kDa is observed when DOLPP1 is expressed in yeast, COS, and Sf9 cells. This study is the first identification and characterization of a cDNA clone encoding an essential component of a mammalian lipid pyrophosphate phosphatase that is highly specific for Dol-P-P. The specificity, subcellular location, and topological orientation of the active site described in the current study strongly support a role for Dolpp1p in the recycling of Dol-P-P discharged during protein N-glycosylation reactions on the luminal leaflet of the endoplasmic reticulum in mammalian cells.The multisubunit complex, oligosaccharyltransferase (1), catalyzes the transfer of Glc 3 Man 9 GlcNAc 2 from dolichyl pyrophosphate (Dol-P-P) 1 to appropriate asparagine residues during the co-translational N-glycosylation of nascent polypeptides in yeast and mammalian cells (2-4). During the primary N-glycosylation reaction, Dol-P-P is released on the luminal surface of the endoplasmic reticulum (ER). In order for Dol-P-P to be re-utilized as a glycosyl carrier lipid for additional rounds of lipid intermediate biosynthesis, it must be converted to dolichyl phosphate (Dol-P) and translocated to the cytoplasmic leaflet of the ER (4). Although it cannot yet be excluded that Dol-P-P, or perhaps Dol-P, diffuses transversely from the luminal leaflet to the cytoplasmic face by a protein-mediated mechanism, it is more likely that it is dephosphorylated on the luminal surface to form free dolichol that could more readily diffuse back to the cytoplasmic leaflet. Cytoplasmically oriented dolichol would then be re-phosphorylated by dolichol kinase (5, 6). Recent studies (7,8) have shown that the CWH8 gene in Saccharomyces cerevisiae encodes a Dol-P-P phosphatase that actively converts Dol-P-P to Dol-P and is also capable of dephosphorylating Dol-P at a slower rate. Moreover, the yeast Dol-P-P phosphatase is recovered in crude microsomal fractions, but its subcellular location has not been established.Although there have been numerous reports (4, 7-13) that crude microsomal fractions from...

Cyclophilin J (CYPJ) is a new member of the peptidyl-prolyl cis/trans-isomerase (PPIase) identified with upregulated expression in human glioma. However, the biological function of CYPJ remained unclear. We aimed to study the role of CYPJ in hepatocellular carcinoma (HCC) carcinogenesis and its therapeutic potential. We determined the expression of CYPJ in HCC/adjacent normal tissues using Western blot, Northern blot and semi-quantitative RT-PCR, analyzed the biochemical characteristics of CYPJ, and resolved the 3D-structure of CYPJ/Cyclosporin A (CsA) complex. We also studied the roles of CYPJ in cell cycle, cyclin D1 regulation, in vitro and in vivo tumor growth. We found that CYPJ expression was upregulated in over 60% HCC tissues. The PPIase activity of CYPJ could be inhibited by the widely used immunosuppressive drug CsA. CYPJ was found expressed in the whole cell of HCC with preferential location at the cell nucleus. CYPJ promoted the transition of cells from G1 phase to S phase in a PPIase-dependent manner by activating cyclin D1 promoter. CYPJ overexpression accelerated liver cell growth in vitro (cell growth assay, colony formation) and in vivo (xenograft tumor formation). Inhibition of CYPJ by its inhibitor CsA or CYPJ-specific RNAi diminished the growth of liver cancer cells in vitro and in vivo. In conclusion, CYPJ could facilitate HCC growth by promoting cell cycle transition from G1 to S phase through the upregulation of cyclin D1. Suppression of CYPJ could repress the growth of HCC, which makes CYPJ a potential target for the development of new strategies to treat this malignancy.