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

Ongusaha, Pat P.; Kim, Hyung Gu; Boswell, Sarah A.; Ridley, Anne J.; Der, Channing J.; Dotto, G. Paolo; Kim, Young–Bum; Aaronson, Stuart A.; Lee, Sam W.

doi:10.1016/j.cub.2006.10.056

Cited by 91 publications

(39 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1C). RhoE, another member of the Rho family, has been identified as a p53-inducible gene in response to genotoxic agents (33). The authors of that study focused on upregulation of RhoE mRNA after long exposures to genotoxic agents, typically 12 h or longer.…”

Section: Resultsmentioning

confidence: 99%

RhoB Promotes γH2AX Dephosphorylation and DNA Double-Strand Break Repair

Mamouni

Cristini

Guirouilh‐Barbat

et al. 2014

Molecular and Cellular Biology

View full text Add to dashboard Cite

c Unlike other Rho GTPases, RhoB is rapidly induced by DNA damage, and its expression level decreases during cancer progression. Because inefficient repair of DNA double-strand breaks (DSBs) can lead to cancer, we investigated whether camptothecin, an anticancer drug that produces DSBs, induces RhoB expression and examined its role in the camptothecin-induced DNA damage response. We show that in camptothecin-treated cells, DSBs induce RhoB expression by a mechanism that depends notably on Chk2 and its substrate HuR, which binds to RhoB mRNA and protects it against degradation. RhoB-deficient cells fail to dephosphorylate ␥H2AX following camptothecin removal and show reduced efficiency of DSB repair by homologous recombination. These cells also show decreased activity of protein phosphatase 2A (PP2A), a phosphatase for ␥H2AX and other DNA damage and repair proteins. Thus, we propose that DSBs activate a Chk2-HuR-RhoB pathway that promotes PP2A-mediated dephosphorylation of ␥H2AX and DSB repair. Finally, we show that RhoB-deficient cells accumulate endogenous ␥H2AX and chromosomal abnormalities, suggesting that RhoB loss increases DSB-mediated genomic instability and tumor progression.

show abstract

Section: Resultsmentioning

confidence: 99%

RhoB Promotes γH2AX Dephosphorylation and DNA Double-Strand Break Repair

Mamouni

Cristini

Guirouilh‐Barbat

et al. 2014

Molecular and Cellular Biology

View full text Add to dashboard Cite

show abstract

“…RhoE-luc, Hey2-luc, HES1-AB-luc, HES1-ΔAB-luc, and CSL-responsive luciferase reporter constructs were previously described (2, 5, 22). …”

Section: Methodsmentioning

confidence: 99%

Small GTPase RhoE/Rnd3 Is a Critical Regulator of Notch1 Signaling

et al. 2014

Self Cite

View full text Add to dashboard Cite

Aberrations of Notch signaling have been implicated in a variety of human cancers. Oncogenic mutations in NOTCH1 are common in human T-cell leukemia and lymphomas. However, loss-of-function somatic mutations in NOTCH1 arising in solid tumors imply a tumor suppressor function, which highlights the need to understand Notch signaling more completely. Here we describe the small GTPase RhoE/Rnd3 as a downstream mediator of Notch signaling in squamous cell carcinomas (SCCs) that arise in skin epithelia. RhoE is a transcriptional target of activated Notch1, which is attenuated broadly in SCC cells. RhoE depletion suppresses Notch1-mediated signaling in vitro, rendering primary keratinocytes resistant to Notch1-mediated differentiation and thereby favoring a proliferative cell fate. Mechanistic investigations indicated that RhoE controls a key step in Notch1 signaling by mediating nuclear translocation of the activated portion of Notch1 (N1IC) through interaction with importins. Our results define RhoE as a Notch1 target that is essential for recruitment of N1IC to the promoters of Notch1 target genes, establishing a regulatory feedback loop in Notch1 signaling. This molecular circuitry may inform distinct cell fate decisions to Notch1 in epithelial tissues where carcinomas such as SCC arise.

show abstract

“…It has been found that Rnd3 is a downstream target of p53, which favors cell survival through the inhibition of ROCK1-mediated apoptosis (100, 156). Ongusaha and co-workers showed that Rnd3 was transcriptionally induced in response to various DNA damaging agents, resulting in the disassembly of actin stress fibers.…”

Section: Physiological Function Of Rnd3mentioning

confidence: 99%

“…Ongusaha and co-workers showed that Rnd3 was transcriptionally induced in response to various DNA damaging agents, resulting in the disassembly of actin stress fibers. Knockdown of Rnd3 not only prevented the disassembly of the actin cytoskeleton, but also promoted apoptosis (100). However, it should be noted that inhibition of ROCK activity does not protect against apoptosis in all cell types, implying that additional factors likely contribute to the ultimate outcome (29).…”

Section: Physiological Function Of Rnd3mentioning

confidence: 99%

Pathophysiological Functions of Rnd 3/ RhoE

Jie

Andrade

Lin

et al. 2015

Comprehensive Physiology

View full text Add to dashboard Cite

Rnd3, also known as RhoE, belongs to the Rnd subclass of the Rho family of small GTP-binding proteins. Rnd proteins are unique due to their inability to switch from a GTP-bound to GDP-bound conformation. Even though studies of the biological function of Rnd3 are far from being concluded, information is available regarding its expression pattern, cellular localization, and its activity, which can be altered depending on the conditions. The compiled data from these studies implies that Rnd3 may not be a traditional small GTPase. The basic role of Rnd3 is to report as an endogenous antagonist of RhoA signaling-mediated actin cytoskeleton dynamics, which specifically contributes to cell migration and neuron polarity. In addition, Rnd3 also plays a critical role in arresting cell cycle distribution, inhibiting cell growth, and inducing apoptosis and differentiation. Increasing data have shown that aberrant Rnd3 expression may be the leading cause of some systemic diseases; particularly highlighted in apoptotic cardiomyopathy, developmental arrhythmogenesis and heart failure, hydrocephalus, as well as tumor metastasis and chemotherapy resistance. Therefore, a better understanding of the function of Rnd3 under different physiological and pathological conditions, through the use of suitable models, would provide a novel insight into the origin and treatment of multiple human diseases.

show abstract

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

Cited by 91 publications

References 27 publications

RhoB Promotes γH2AX Dephosphorylation and DNA Double-Strand Break Repair

RhoB Promotes γH2AX Dephosphorylation and DNA Double-Strand Break Repair

Small GTPase RhoE/Rnd3 Is a Critical Regulator of Notch1 Signaling

Pathophysiological Functions of Rnd 3/ RhoE

Contact Info

Product

Resources

About