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The goal of the article is analysis of the structure and dynamics of indirect taxes for the previous five years and also the influence of indirect taxation upon formation of income of the State Budget of Ukraine. The article analyses the modern state of indirect taxation in Ukraine. Specific weight of the value added tax, excise tax and customs duty are considered in the structure of tax receipts of the consolidated budget of Ukraine as indirect taxes. The article shows that receipts of the State Budget of Ukraine are mostly provided by indirect taxes. The Ukrainian taxation system is mostly a factor of reduction of the level of economic growth and investment activity in the country and the existing system of administering is not completely capable of excluding the possibility of tax evasion. The prospect of further studies in this direction is improvement of organisation of tax control in Ukraine and differentiation of the value added tax rates depending on the level of consumption of goods and level of income of consumers.

Renal cell carcinomas (RCC) commonly retain wild-type but functionally inactive p53, which is repressed by an unknown dominant mechanism. To help reveal this mechanism, we screened a diverse chemical library for small molecules capable of restoring p53-dependent transactivation in RCC cells carrying a p53-responsive reporter. Among the compounds isolated were derivatives of 9-aminoacridine (9AA), including the antimalaria drug quinacrine, which strongly induced p53 function in RCC and other types of cancer cells. Induction of p53 by these compounds does not involve genotoxic stress and is mediated by suppression of NF-[kappa]B activity. In contrast to agents that target I[kappa]B kinase 2, 9AA and quinacrine can effectively suppress both basal and inducible activities of NF-[kappa]B, representing inhibitors of a previously undescribed type that convert NF-[kappa]B from a transactivator into a transrepressor, leading to accumulation of inactive nuclear complexes with unphosphorylated Ser-536 in the p65/ReIA subunit, p53 function in RCC can be restored by ectopic expression of a superrepressor of hob as effectively as by 9AA-derived compounds. These findings suggest that the complete or partial repression of p53 observed in many tumors can be the result of constitutive activation of NF-[kappa]B. The results demonstrate, in principle, the possibility to kill cancer cells selectively through simultaneous inhibition of NF-[kappa]B and activation of p53 by a single small molecule and suggest anticancer applications for the well known antimalaria drug quinacrine. anticancer treatment | apoptosis | chemical library | quinacrine

Human prothymosin alpha (ProT alpha), an acidic nuclear protein, in its native unfolded state is discussed relative to its adoption of a partially folded collapsed conformation at acidic pH. Structural properties in the compact denatured state it assumes are different from those it has as a molten globule. The conformational changes may be associated with the protein activities.

Renal cell carcinomas (RCC) commonly retain wild-type but functionally inactive p53, which is repressed by an unknown dominant mechanism. To help reveal this mechanism, we screened a diverse chemical library for small molecules capable of restoring p53-dependent transactivation in RCC cells carrying a p53-responsive reporter. Among the compounds isolated were derivatives of 9-aminoacridine (9AA), including the antimalaria drug quinacrine, which strongly induced p53 function in RCC and other types of cancer cells. Induction of p53 by these compounds does not involve genotoxic stress and is mediated by suppression of NF-κB activity. In contrast to agents that target IκB kinase 2, 9AA and quinacrine can effectively suppress both basal and inducible activities of NF-κB, representing inhibitors of a previously undescribed type that convert NF-κB from a transactivator into a transrepressor, leading to accumulation of inactive nuclear complexes with unphosphorylated Ser-536 in the p65/ReIA subunit. p53 function in RCC can be restored by ectopic expression of a superrepressor of IκB as effectively as by 9AA-derived compounds. These findings suggest that the complete or partial repression of p53 observed in many tumors can be the result of constitutive activation of NF-κB. The results demonstrate, in principle, the possibility to kill cancer cells selectively through simultaneous inhibition of NF-κB and activation of p53 by a single small molecule and suggest anticancer applications for the well known antimalaria drug quinacrine. [ABSTRACT FROM AUTHOR]