[Show abstract][Hide abstract] ABSTRACT: Previous studies have demonstrated that autophagy is involved in the pathogenesis of human cytomegalovirus (HCMV) infection. However, whether autophagy is regulated by murine cytomegalovirus (MCMV) infection has not yet been investigated. The purpose of these studies was to determine how autophagy is affected by MCMV infection of the retinal pigment epithelial (RPE) cells and whether there is a functional relationship between autophagy and apoptosis; and if so, how regulation of autophagy impacts apoptosis.
[Show abstract][Hide abstract] ABSTRACT: A high frequency of human cytomegalovirus (HCMV) genome and antigens in tumor samples of patients with different malignancies is now well documented, although the causative role for HCMV in the development of the neoplasias remains to be established. HCMV infection can modulate multiple cellular regulatory and signalling pathways in a manner similar to that of oncoproteins of small DNA tumor viruses such as human papilloma virus or adenoviruses. However, in contrast to these DNA tumor viruses, HCMV infection fails to transform susceptible normal human cells. There is now growing evidence that tumor cells with disrupted regulatory and signalling pathways enable HCMV to modulate their properties including stimulation of cell proliferation, survival, invasion, production of angiogenic factors, and immunogenic properties. In contrast to previously suggested "hit and run" transformation we suggest that persistence in tumor cells is essential for HCMV to fully express its oncomodulatory effects. These effects are observed particularly in persistent HCMV infection and are mediated mainly by activity of HCMV regulatory proteins. In persistently HCMV-infected tumor cell lines - a selection of novel, slowly growing virus variants with changes in coding sequences for virus regulatory proteins takes place. As a result, oncomodulatory effects of HCMV infection may lead to a shift to more malignant phenotype of tumor cells contributing to tumor progression.
[Show abstract][Hide abstract] ABSTRACT: Protein kinases are central components of signal transduction cascades often dysregulated in cancer, and they represent some of the most promising drug targets. However, the target selectivity is a major concern because most described kinase inhibitors target the highly conserved ATP-binding pocket. Recently, new classes of inhibitors that do not compete with ATP and exhibit different mechanisms of action have been described. Overexpression of protein kinase CK2 is an unfavorable prognostic marker in several cancers. Consequently, CK2 has emerged as a relevant therapeutic target. Several classes of ATP-competitive inhibitors have been identified, showing variable effectiveness. The molecular architecture of this multisubunit enzyme could offer alternative strategies to inhibit CK2 functions, and this review illustrates these emerging possibilities.
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