In 2007, the International Knockout Mouse Consortium (IKMC) made the ambitious promise to generate mutations in virtually every protein-coding gene of the mouse genome in a concerted worldwide action. Now, 5 years later, the IKMC members have developed high-throughput gene trapping and, in particular, gene-targeting pipelines and generated more than 17,400 mutant murine embryonic stem (ES) cell clones and more than 1,700 mutant mouse strains, most of them conditional. A common IKMC web portal (www.knockoutmouse.org) has been established, allowing easy access to this unparalleled biological resource. The IKMC materials considerably enhance functional gene annotation of the mammalian genome and will have a major impact on future biomedical research.
(Androphy et al., 1987; Dostatni et al., 1988;McBride Sylvain Goyat, Moshe Yaniv and et al., 1989). Franç oise Thierry 1Bovine papillomavirus type 1 (BPV-1) has been studied condylomas. In HPV18, the viral transforming genes E6 level of cell death by apoptosis and G 1 arrest. Overand E7 are expressed from a single promoter, termed P 105 , expression of a p53 trans-dominant-negative mutant which is regulated by an upstream 800 bp long control abolished both E2-induced p53 transcriptional activregion (LCR) (Thierry et al., 1987a). This region contains ation and E2-mediated G 1 growth arrest, but showed a keratinocyte-specific enhancer, upstream of promoter no effect on E2-triggered apoptosis. These results sugelements (TATA and Sp1) crucial for transcription (Garciagest that the effects of E2 on cell cycle progression Carranca et al., 1988). Four E2 binding sites are located and cell death follow distinct pathways involving two in the LCR, two of which lie within the promoter, tightly different functions of p53.flanked 5Ј by the Sp1 and 3Ј by the TATA motifs. Keywords: apoptosis/cell cycle/HPV18 E2/p53/ The HPV18 promoter has been shown to be strongly transcription repressed by the BPV-1 E2 and E2TR proteins which presumably hinder the formation of the transcription initiation complex (Thierry and Yaniv, 1987; Dostatni et al., 1991). A moderate repression is also observed with
We have previously shown that expression of the papillomavirus E2 protein in HeLa cells induces p53 accumulation and causes both cell cycle arrest and apoptosis. In contrast to growth arrest, onset of apoptosis was not correlated with an increase of p53 transcriptional activity. In the present study, we conducted biochemical and genetic experiments in order to determine whether E2-induced apoptosis was independent of p53 induction. We showed that E2 did not alter the transcription of Bax, a known p53-activated cell death inducer. The time course of apoptotic cell death preceded p53 induction by several hours. Overexpression of the HPV18 E6 oncogene prevented E2-mediated p53 accumulation, but did not alter the rate of cell death. Finally, point mutants of the HPV18 E2 transactivation domain induced apoptosis, although they were unable to induce high p53 accumulation or cell cycle arrest. In addition, the results obtained with these mutants indicated that both transcriptional activation and replication functions of E2 were dispensable for the induction of cell death. These observations show that E2-induced apoptosis is an early event, independent of p53 accumulation and unrelated to downstream p53-dependent transcriptional events.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.