Human EHMT2/G9a activates p53 through methylation-independent mechanism

p53 is a critical tumor suppressor in humans. It functions mostly as a transcriptional factor and its activity is regulated by numerous post-translational modifications. Among different covalent modifications found on p53 the most controversial one is lysine methylation. We found that human G9a (hG9a) unlike its mouse orthologue (mG9a) potently stimulated p53 transcriptional activity. Both ectopic and endogenous hG9a augmented p53-dependent transcription of pro-apoptotic genes, including Bax and Puma, resulting in enhanced apoptosis and reduced colony formation. Significantly, shRNA-mediated knockdown of hG9a attenuated p53-dependent activation of Puma. On the molecular level, hG9a interacted with histone acetyltransferase, p300/CBP, resulting in increased histone acetylation at the promoter of Puma. The bioinformatics data substantiated our findings showing that positive correlation between G9a and p53 expression is associated with better survival of lung cancer patients. Collectively, this study demonstrates that depending on the cellular and organismal context, orthologous proteins may exert both overlapping and opposing functions. Furthermore, this finding has important ramifications on the use of G9a inhibitors in combination with genotoxic drugs to treat p53-positive tumors.Oncogene advance online publication, 25 July 2016; doi:10.1038/onc.2016.258

The Alkaline Hydrolysis of Sulfonate Esters: Challenges in Interpreting Experimental and Theoretical Data

Sulfonate ester hydrolysis has been the subject of recent debate, with experimental evidence interpreted in terms of both stepwise and concerted mechanisms. In particular, a recent study of the alkaline hydrolysis of a series of benzene arylsulfonates (Babtie et al., Org. Biomol. Chem. 10, 2012, 8095) presented a nonlinear Brønsted plot, which was explained in terms of a change from a stepwise mechanism involving a pentavalent intermediate for poorer leaving groups to a fully concerted mechanism for good leaving groups and supported by a theoretical study. In the present work, we have performed a detailed computational study of the hydrolysis of these compounds and find no computational evidence for a thermodynamically stable intermediate for any of these compounds. Additionally, we have extended the experimental data to include pyridine-3-yl benzene sulfonate and its N-oxide and N-methylpyridinium derivatives. Inclusion of these compounds converts the Brønsted plot to a moderately scattered but linear correlation and gives a very good Hammett correlation. These data suggest a concerted pathway for this reaction that proceeds via an early transition state with little bond cleavage to the leaving group, highlighting the care that needs to be taken with the interpretation of experimental and especially theoretical data

IMPACT ON STAFF LOYALTY performance of the company

В статье исследуется влияние лояльности персонала ЗАО «Крафтвэй корпорэйшн ПЛС» на эффективность работы компании. Рассмотрены основные подходы к определению понятия «лояльность персонала компании» и его практические аспекты. Проанализированы методики определения уровня лояльности персонала. По предложенной методике исследован уровень лояльности персонала ЗАО «Крафтвэй корпорэйшн ПЛС», а также разработаны рекомендации по ее повышению. Практическая значимость исследования заключается в возможности использования его предложений и выводов в управлении лояльностью персонала различных компаний.The article examines the impact of staff loyalty JSC “Kraftway Corporation PLC” on the performance of the company. The main approaches to the definition of “loyalty to the company staff “ and its practical aspects. Analyzed the methodology for determining the level of staff loyalty. According to the proposed method is investigated level of loyalty of personnel of “Kraftway Corporation PLC” as well as recommendations on its increase. The practical significance of the study is the ability to use his proposals and conclusions in loyalty management personnel of different companies