USP15 regulates dynamic protein-protein interactions of the spliceosome through deubiquitination of PRP31.

Post-translational modifications contribute to the spliceosome dynamics by facilitating the physical rearrangements of the spliceosome. Here, we report USP15, a deubiquitinating enzyme, as a regulator of protein-protein interactions for the spliceosome dynamics. We show that PRP31, a component of U4 snRNP, is modified with K63-linked ubiquitin chains by the PRP19 complex and deubiquitinated by USP15 and its substrate targeting factor SART3. USP15SART3 makes a complex with USP4 and this ternary complex serves as a platform to deubiquitinate PRP31 and PRP3. The ubiquitination and deubiquitination status of PRP31 regulates its interaction with the U5 snRNP component PRP8, which is required for the efficient splicing of chromosome segregation related genes, probably by stabilizing the U4/U6.U5 tri-snRNP complex. Collectively, our data suggest that USP15 plays a key role in the regulation of dynamic protein-protein interactions of the spliceosome

Cancer Statistics in Korea: Incidence, Mortality, Survival, and Prevalence in 2008

PURPOSE: This paper overviews the nationwide cancer statistics including incidence, mortality, survival and prevalence, and their trends in Korea based on the year 2008 cancer incidence data. MATERIALS AND METHODS: Incidence data from 1993 to 2008 were obtained from the Korea National Cancer Incidence Database, and the vital status was followed through December 31, 2009. Mortality data from 1983 to 2008 were obtained from the Korea National Statistics Office. Crude rates and age-standardized rates for incidence, mortality, prevalence and relative survival were calculated. RESULTS: There were 178,816 cancer cases and 68,912 cancer deaths observed during year 2008 and 724,663 10-year cancer prevalent cases as of January 1, 2009 in Korea. The incidence rate for all cancer combined showed an annual increase of 3.1% from 1999 to 2008. CONCLUSION: With significantly increasing cancer incidence, Korea faces a large cancer burden and efficient cancer control programs are essential.ope

Prediction of Cancer Incidence and Mortality in Korea, 2011

PURPOSE: To estimate the current cancer burden in Korea, cancer incidence and mortality were projected for the year 2011. MATERIALS AND METHODS: The cancer incidence data from 1999-2008 were obtained from the Korea National Cancer Incidence Database, and the cancer mortality data from 1993-2009 were obtained from the Korea National Statistics Office. Cancer incident cases and rates in 2011 were projected from fitting a linear regression model on observed age-specific cancer incidence rates against observed years, then multiplying the projected age-specific rates by the age-specific population. For cancer mortality, a similar procedure was applied for projection except that a Joinpoint regression model was used to determine at which year the linear trend significantly changed. RESULTS: A total of 216,809 new cancer cases and 71,036 cancer deaths are projected to occur in Korea in 2011. For all sites combined, the crude incidence rates are projected to be 437.9 and 420.5 and the age-standardized incidence rates are projected to be 336.5 and 279.7 per 100,000 for men and women, respectively. CONCLUSION: Cancer has become an important public health concern in Korea, and as Korea becomes an aged society, the cancer burden will continue to increase.ope

Negative regulation of ERα by a novel protein CAC1 through association with histone demethylase LSD1

AbstractERα, a critical transcriptional factor for breast cancer proliferation, is regulated by a complex binding repertoire that includes coactivators and corepressors. Here, we identified a novel class of ERα coregulator called CAC1. The CoRNR box of CAC1 was required for the binding to and inactivation of ERα. CAC1 also associated with histone demethylase LSD1 and suppressed LSD1-enhanced ERα activity. CAC1 impaired recruitment of ERα and LSD1 to the ERα-responsive promoter, leading to greater H3K9me3 accumulation. This effect was reversed by CAC1 depletion. Finally, CAC1 increased paclitaxel-induced cell death in ERα-positive MCF7 cells, which are paclitaxel-resistant. Overall, our study provides the first evidence that CAC1, associated with LSD1, functions as an ERα corepressor, implicating a potential antitumor target in ERα-positive breast cancer.Structured summary of protein interactionsER-alpha physically interacts with CAC1 by anti tag coimmunoprecipitation (View Interaction: 1, 2, 3)LSD1 physically interacts with CAC1 by anti tag coimmunoprecipitation (View interaction)CAC1 binds to ER-alpha by pull down (View interaction)CAC1 and ER-alpha colocalizebyfluorescence microscopy (View interaction

CHF Enhancement of Advanced 37-Element Fuel Bundles

A standard 37-element fuel bundle (37S fuel bundle) has been used in commercial CANDU reactors for over 40 years as a reference fuel bundle. Most CHF of a 37S fuel bundle have occurred at the elements arranged in the inner pitch circle for high flows and at the elements arranged in the outer pitch circle for low flows. It should be noted that a 37S fuel bundle has a relatively small flow area and high flow resistance at the peripheral subchannels of its center element compared to the other subchannels. The configuration of a fuel bundle is one of the important factors affecting the local CHF occurrence. Considering the CHF characteristics of a 37S fuel bundle in terms of CHF enhancement, there can be two approaches to enlarge the flow areas of the peripheral subchannels of a center element in order to enhance CHF of a 37S fuel bundle. To increase the center subchannel areas, one approach is the reduction of the diameter of a center element, and the other is an increase of the inner pitch circle. The former can increase the total flow area of a fuel bundle and redistributes the power density of all fuel elements as well as the CHF. On the other hand, the latter can reduce the gap between the elements located in the middle and inner pitch circles owing to the increasing inner pitch circle. This can also affect the enthalpy redistribution of the fuel bundle and finally enhance CHF or dry-out power. In this study, the above two approaches, which are proposed to enlarge the flow areas of the center subchannels, were considered to investigate the impact of the flow area changes of the center subchannels on the CHF enhancement as well as the thermal characteristics by applying a subchannel analysis method