Wnt/-catenin signaling plays critical roles in embryonic development and disease. Here, we identify RNF220, a RING domain E3 ubiquitin ligase, as a new regulator of -catenin. RNF220 physically interacts with -catenin, but instead of promoting its ubiquitination and proteasomal degradation, it stabilizes -catenin and promotes canonical Wnt signaling. Our analysis showed that RNF220 interacts with USP7, a ubiquitin-specific peptidase, which is required for RNF220 to stabilize -catenin. The RNF220/USP7 complex deubiquitinates -catenin and enhances canonical Wnt signaling. Interestingly, the stability of RNF220 itself is negatively regulated by Gsk3, which is a key component of the -catenin destruction complex and is inhibited upon Wnt stimulation. Accordingly, the RNF220/USP7 complex works as a positive feedback regulator of -catenin signaling. In colon cancer cells with stimulated Wnt signaling, knockdown of RNF220 or USP7 impairs Wnt signaling and expression of Wnt target genes, suggesting a potentially novel role of RNF220 in Wnt-related tumorigenesis.
Background: Aromatic rice is popular worldwide because of its characteristic fragrance. Genetic studies and physical fine mapping reveal that a candidate gene (fgr/OsBADH2) homologous to betaine aldehyde dehydrogenase is responsible for aroma metabolism in fragrant rice varieties, but the direct evidence demonstrating the functions of OsBADH2 is lacking. To elucidate the physiological roles of OsBADH2, sequencing approach and RNA interference (RNAi) technique were employed to analyze allelic variation and functions of OsBADH2 gene in aroma production. Semi-quantitative, real-time reverse transcription-polymerase chain reaction (RT-PCR), as well as gas chromatography-mass spectrometry (GC-MS) were conducted to determine the expression levels of OsBADH2 and the fragrant compound in wild type and transgenic OsBADH2-RNAi repression lines, respectively.
Objectives:To study the dynamics of HIV drug resistance (HIVDR) and its association with virologic and immunologic failure as well as mortality among patients on combination antiretroviral therapy (cART) in China.Design:We recruited 365 patients on cART in two rural Chinese counties in 2003–2004 and followed them every 6 months until May 2010.Methods:Virologic failure, HIVDR, immunologic failure and death were documented. We used Kaplan–Meier and the proportional hazards models to identify the timing of the events, and risk factors for mortality.Results:At the end of study, patients had been followed for 1974.3 person-years, a median of 6.1 years. HIVDR mutations were found in 235 (64.4%) patients and 75 died (20.5%, 3.8/100 person-years). Median time from cART to detection of virologic failure was 17.5 months, to HIVDR 36.6 months and to immunologic failure 55.2 months (≈18-month median interval between each adverse milestone). Being male, having a baseline CD4+ cell count of less than 50 cells/μl and HIVDR were associated with higher mortality. Patients who developed HIVDR in the first year of treatment had higher mortality than those developing HIVDR later (adjusted hazard ratio 1.90, 95% confidence interval 1.01–3.48).Conclusion:HIVDR was common and was associated with higher mortality among Chinese patients on cART, particular when HIVDR was detected early in therapy. Our study reinforces the importance of improving patient adherence to cART in order to delay the emergence of HIVDR and obviate the need to switch to costly second-line drug regimens too early.
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