RhoE Is a Pro-Survival p53 Target Gene that Inhibits ROCK I-Mediated Apoptosis in Response to Genotoxic Stress

Abstract

It has been brought to the authors' attention that incorrect images for Figure 2A and the left panel of Figure 4D were selected during the figure preparations for this article. We thus provide corrected versions of Figures 2 and 4 here.In the originally published Figure 2A ''Expression of RhoE protein and mRNA in RhoE knockdown cells,'' the northern blot panel for the loading control (36B4) does not match the experimental conditions described in the figure. It has been pointed out to us that this panel is very similar to Figure 4A in another of our publications (J. Biol. Chem. 279, 38597-38602; September 10, 2004). It is possible that this is an inadvertent duplication, but at this point we regrettably cannot confirm or disprove this. Therefore, the experiments have been repeated, and the new Figure 2A is shown here.In addition, in the originally published Figure 4D ''Effect of ROCK I inhibitor (Y-27632) on CPT-mediated apoptosis,'' the panel for DMSO control (0.1% apoptosis) was misplaced in the next panel for Y-27632-treated control (0.3% apoptosis). In order to ensure integrity of the data, the experiments have been repeated, and the results reproducing the original data are shown in the new Figure 4D here.

Plakoglobin-dependent regulation of keratinocyte APOPTOSIS by Rnd3

“…1B). This would be consistent with previously published data in which knockdown of ROCK1 expression or treatment with Y-27632 protected U2OS cells from camptothecin-induced cell death (Ongusaha et al, 2006).…”

“…There are a number of reports that implicate Rnd3 in regulation of apoptosis; increased expression of Rnd3 has been reported in cells treated with various apoptosis-inducing stimuli and over-expression of Rnd3 increases the basal rate of apoptosis (Villalonga et al, 2004;Bektic et al, 2005;Poch et al, 2007). However, it should be noted that other reports have described a pro-survival function for Rnd3 whereby use of siRNA to prevent Rnd3 induction by apoptotic agents lead to cell death (Ongusaha et al, 2006;Boswell et al, 2007). We did not observe an increase in Rnd3 expression following treatment with cisplatin and one possible explanation for this might be the p53 status of HaCaT cells.…”

“…Caspase-mediated cleavage of ROCK1 is known to induce membrane blebbing, nuclear fragmentation and packaging of nuclear material into blebs at the cell surface and treatment of cells with the ROCKI/II inhibitor, Y-27632, has been shown to prevent ROCK1-induced membrane blebbing (Coleman et al, 2001;Sebbagh et al, 2001). Similarly, Y-27632 has also been shown to protect U2OS cells from camptothecin-induced apoptosis and reduce endotoxininduced apoptosis in the liver (Ongusaha et al, 2006;Thorlacius et al, 2006). Rnd3 is a known substrate for ROCK1 and we observe that, in addition to protecting cells from apoptosis, prolonged treatment with Y-27632 also results in a decrease in Rnd3 expression.…”

“…As Rnd3 is a known ROCK1 binding partner (Riento et al, 2003) and has been implicated in having a role in apoptosis (Bektic et al, 2005;Ongusaha et al, 2006;Boswell et al, 2007;Poch et al, 2007) Rnd3 expression was analysed in cells treated with Y-27632 (Fig. 1C).…”

The Codon 72 Polymorphism of p53 Regulates Interaction with NF-κB and Transactivation of Genes Involved in Immunity and Inflammation

“…In this table, the ratio of P72/R72 induction of each gene is presented at 2 and 4 h after gamma radiation and ranges from 1.4-to 2.9-fold. Several of these genes (Gdf15, Rnd3, Csf-1, and Cxcl1) are known to be upregulated by p53 (29,31,56,57). Interestingly, 10 out of 12 of these genes are known or postulated NF-B target genes (see, for example, http://bioinfo.lifl.fr/NF-KB/), suggesting the involvement of this transcription factor.…”