p27 Deficiency Cooperates with Bcl-2 but Not Bax to Promote T-Cell Lymphoma

The effect of Bcl-2 on oncogenesis is complex and expression may either delay or accelerate oncogenesis. The pro-oncogenic activity is attributed to its well characterized anti-apoptotic function while the anti-oncogenic function has been attributed to its inhibition of cellular proliferation. Recent studies demonstrate that p27 may mediate the effects of Bcl-2 on cellular proliferation. We hypothesized that p27 may suppress tumor formation by Bcl-2 family members. To test this hypothesis, cell cycle inhibition and lymphoma development were examined in Lck-Bcl-2 and Lck-Bax38/1 transgenic mice deficient in p27. Strikingly, p27 deficiency synergistically cooperates with Bcl-2 to increase T cell hyperplasia and development of spontaneous T cell lymphomas. Within 1 year, >90% of these mice had developed thymic T cell lymphomas. This high penetrance contrasts with a one year incidence of <5% of thymic lymphoma in Lck-Bcl-2 or p27 −/− mice alone. In contrast, p27 deficiency had no effect on tumor formation in Lck-Bax38/1 transgenic mice, another model of T cell lymphoma. Histologically the lymphomas in p27 −/− Lck-Bcl-2 mice are lymphoblastic and frequently involve multiple organs suggesting an aggressive phenotype. Interestingly, in mature splenic T cells, Bcl-2 largely retains its anti-proliferative function even in the absence of p27. T cells from p27 −/− Lck-Bcl-2 mice show delayed kinetics of CDK2 Thr-160 phosphorylation. This delay is associated with a delay in the up regulation of both Cyclin D2 and D3. These data demonstrate a complex relationship between the Bcl-2 family, cellular proliferation, and oncogenesis and demonstrate that p27 up-regulation is not singularly important in the proliferative delay observed in T cells expressing Bcl-2 family members. Nonetheless, the results indicate that p27 is a critical tumor suppressor in the context of Bcl-2 expression

FORMATION AND MANAGEMENT OF THE CLIENT BASE OF BANK

The relevance of the topic of the article is due to the fact that the priority of a modern commercial bank is the effective management of its own customer base through an effective customer policy. The profits that a commercial bank strives for are provided by the banking operations provided by the bank to its customers. Therefore, achieving this goal is impossible without the formation, maintenance and expansion of its own quality customer base. In addition, it is in a period of unstable economic situation, when there is a decline in income of Ukrainian consumers of banking services, inflationary expectations increase and distrust of financial institutions, the formation and implementation of effective customer policy of a commercial bank become particularly relevant. But the changing economic situation and the development of the banking business require further research in this area and the development of corrections in the current customer strategy of the bank. The subject of the research is the formation and management of the customer base of Ukrsibbank. The object of study is the economic relations that arise in the process of forming the customer base of the bank and its management. The purpose of the article is to identify scientific and methodological approaches and recommendations that will contribute to more effective management of the customer base of bank. The task of the work is to substantiate the division of the bank's customer base into segments as an object of management in the bank. After analyzing the information obtained, it is possible to explore the conceptual basis for the formation of a customer base management system because the basics of its formation is an important step to make promising recommendations for the formation of strategies for establishing cooperation with different groups of customers. According to the results of the research, the existing scientific and methodological approaches to defining the customer base as an object of management in the bank are obtained. The conceptual bases of formation of the bank's customer base management system are analyzed, give an opportunity to develop recommendations for the formation of strategies for establishing cooperation between the bank and various groups of customers. The obtained results can be used for future effective implementation of the customer-oriented management system in bank

Bcl-x(L)/Bcl-2 coordinately regulates apoptosis, cell cycle arrest and cell cycle entry

Bcl-x(L) and Bcl-2 inhibit both apoptosis and proliferation. In investigating the relationship between these two functions of Bcl-x(L) and Bcl-2, an analysis of 24 Bcl-x(L) and Bcl-2 mutant alleles, including substitutions at residue Y28 previously reported to selectively abolish the cell cycle activity, showed that cell cycle delay and anti-apoptosis co-segregated in all cases. In determining whether Bcl-2 and Bcl-x(L) act in G(0) or G(1), forward scatter and pyronin Y fluorescence measurements indicated that Bcl-2 and Bcl-x(L) cells arrested more effectively in G(0) than controls, and were delayed in G(0)–G(1) transition. The cell cycle effects of Bcl-2 and Bcl-x(L) were reversed by Bad, a molecule that counters the survival function of Bcl-2 and Bcl-x(L). When control and Bcl-x(L) cells of equivalent size and pyronin Y fluorescence were compared, the kinetics of cell cycle entry were similar, demonstrating that the ability of Bcl-x(L) and Bcl-2 cells to enhance G(0) arrest contributes significantly to cell cycle delay. Our data suggest that cell cycle effects and increased survival both result from intrinsic functions of Bcl-2 and Bcl-x(L)