Genetic response to DNA damage: Proapoptotic targets of RhoB include modules for p53 response and susceptibility to alzheimer's disease

Knockout mouse studies indicate that the small GTPase RhoB is critical for apoptosis triggered by genotoxic stress in transformed mouse cells. However, the mechanisms used by RhoB to sensitize cells to cell death are obscure. To gain insight into this question, we compared the genetic response of ce...

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Bibliographic Details
Published inCancer biology & therapy Vol. 4; no. 3; pp. 282 - 288
Main Authors Kamasani, Uma, Prendergast, George C.
Format Journal Article
LanguageEnglish
Published United States Taylor & Francis 01.03.2005
Subjects
Alzheimer Disease - genetics
Animals
Antibiotics, Antineoplastic - pharmacology
Apoptosis - genetics
Binding
Biology
Bioscience
Calcium
Cancer
Cell
Cell Adhesion - genetics
Cycle
Cytoskeleton - genetics
DNA - drug effects
DNA Damage - genetics
Doxorubicin - pharmacology
Gene Expression Regulation
Genetic Predisposition to Disease
Immunity - genetics
Landes
Mice
Mice, Knockout
Oligonucleotide Array Sequence Analysis
Organogenesis
Protein Biosynthesis - genetics
Proteins
rhoB GTP-Binding Protein - genetics
rhoB GTP-Binding Protein - physiology
Tumor Suppressor Protein p53 - metabolism
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Summary:Knockout mouse studies indicate that the small GTPase RhoB is critical for apoptosis triggered by genotoxic stress in transformed mouse cells. However, the mechanisms used by RhoB to sensitize cells to cell death are obscure. To gain insight into this question, we compared the genetic response of cells with different rhoB genotypes to the DNA damaging anticancer drug doxorubicin (DOX). The microarray hybridization strategy focused on events occurring by 6 hr of DOX treatment, preceding the execution phase of RhoB-dependent apoptosis by 12-16 hr. Genes controlling cytoskeletal organization, adhesion, transcription, trafficking, apoptosis, and protein turnover were represented prominently. Gene clustering revealed a module of p53 target genes, suggesting that RhoB may modify the p53 response, and a module for susceptibility to Alzheimer's disease, suggesting a link between RhoB and age-associated dementia. The findings of this study suggest mechanisms by which RhoB may act to elevate the sensitivity of cells to apoptosis following genotoxic stress.
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ISSN:1538-4047
1555-8576
DOI:10.4161/cbt.4.3.1498