The phosphatidyl inositol 3 kinase pathway does not suppress activation of the ARF and BIM genes by deregulated E2F1 activity.

The transcription factor E2F plays crucial roles in tumor suppression by activating pro-apoptotic genes such as the tumor suppressor ARF. The regulation of the ARF gene is distinct from that of growth-related E2F targets, in that it is specifically activated by deregulated E2F activity, induced by over-expression of E2F or forced inactivation of pRB, but not by physiological E2F activity induced by growth stimulation. The phosphatidyl inositol 3 kinase (PI3K) pathway was reported to suppress expression of some atypical pro-apoptotic genes by over-expressed E2F1. However, the effects of the PI3K pathway on the distinct regulation of typical pro-apoptotic E2F targets have not been elucidated. We examined whether the PI3K pathway suppressed activation of the typical pro-apoptotic E2F targets ARF and BIM. Activation of the PI3K pathway by growth stimulation or introduction of a constitutively active Akt/PKB did not reduce induction of ARF or BIM gene expression or activation of their promoters by over-expressed E2F1. These results suggest that the PI3K pathway does not suppress induction of typical pro-apoptotic genes that are selectively activated by deregulated E2F1.

Usability of an Alcohol Disinfectant Containing Organic Acids and Metal Salt for Environmental Surfaces.

Environmental cleaning and disinfection plays an important role as a part of the standard precautions to prevent healthcare-associated infections, whereas hand hygiene is one of the most important strategies for breaking the chain of transmission. Cleaning and disinfection of high-touch areas in a health-care facility is emphasized. And wiping with an alcohol-saturated cloth which has features such as low corrosion and a wide range of antimicrobial activity is performed commonly for this purpose. Although alcohol provides immediate activity against enveloped viruses, its virucidal activity against certain non-enveloped viruses, including norovirus, is insufficient. We created a novel alcohol-based hand rub, MR06B7, which is safe for the skin, and is active against an extended spectrum of microorganisms including non-enveloped viruses. For environmental surface disinfection, a novel disinfectant MR13B15, which is based on MR06B7, has been developed. In vitro antimicrobial activity against a variety of pathogens, material compatibility, and simulated surface disinfection and decontamination efficacy of MR13B15 were investigated. According to the results, MR13B15 demonstrated potent bactericidal, fungicidal, mycobactericidal, and virucidal activity within a short contact time in addition to superior efficacy against non-enveloped viruses compared to ethanol for disinfection. Moreover, MR13B15 showed better material compatibility. Two simulation tests conducted for evaluating the disinfection and decontamination potency on environmental surfaces against feline calicivirus, a surrogate for norovirus, indicated that MR13B15 had superior efficacy for surface treatment compared to ethanol. These findings suggest that MR13B15, which satisfies most requirements of an environmental surface disinfectant, may contribute to accomplishing advanced standard precautions in preventing infections.

Identification of novel target genes specifically activated by deregulated E2F in human normal fibroblasts.

The transcription factor E2F is the principal target of the tumor suppressor pRB. E2F plays crucial roles not only in cell proliferation by activating growth-related genes but also in tumor suppression by activating pro-apoptotic and growth-suppressive genes. We previously reported that, in human normal fibroblasts, the tumor suppressor genes ARF, p27(Kip1) and TAp73 are activated by deregulated E2F activity induced by forced inactivation of pRB, but not by physiological E2F activity induced by growth stimulation. In contrast, growth-related E2F targets are activated by both E2F activities, underscoring the roles of deregulated E2F in tumor suppression in the context of dysfunctional pRB. In this study, to further understand the roles of deregulated E2F, we explored new targets that are specifically activated by deregulated E2F using DNA microarray. The analysis identified nine novel targets (BIM, RASSF1, PPP1R13B, JMY, MOAP1, RBM38, ABTB1, RBBP4 and RBBP7), many of which are involved in the p53 and RB tumor suppressor pathways. Among these genes, the BIM gene was shown to be activated via atypical E2F-responsive promoter elements and to contribute to E2F1-mediated apoptosis. Our results underscore crucial roles of deregulated E2F in growth suppression to counteract loss of pRB function.