p53 Binding to Target Sites Is Dynamically Regulated Before and After Ionizing Radiation-Mediated DNA Damage

Crosby, Meredith E.; Oancea, Marcela; Almasan, Alexandru

doi:10.1615/jenvpathtoxoncol.v23.i1.70

Cited by 11 publications

(6 citation statements)

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“…Our ChIP data suggested ubiquitous recruitment of Sin3B/HDAC1 on three p53-repressed promoters viz HSPA8 , MAD1 and CRYZ. Previous studies have suggested a dynamic binding of p53 to its target sites before and after stress/DNA damage [37]–[39]. Consistent with these finding, we also show recruitment of p53 and Sin3B at the p53-target sites both before and after Adriamycin treatment.…”

Section: Discussionsupporting

confidence: 92%

Tumor Suppressor Protein p53 Recruits Human Sin3B/HDAC1 Complex for Down-Regulation of Its Target Promoters in Response to Genotoxic Stress

Bansal

Kadamb²,

Mittal³

et al. 2011

PLoS ONE

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Master regulator protein p53, popularly known as the “guardian of genome” is the hub for regulation of diverse cellular pathways. Depending on the cell type and severity of DNA damage, p53 protein mediates cell cycle arrest or apoptosis, besides activating DNA repair, which is apparently achieved by regulation of its target genes, as well as direct interaction with other proteins. p53 is known to repress target genes via multiple mechanisms one of which is via recruitment of chromatin remodelling Sin3/HDAC1/2 complex. Sin3 proteins (Sin3A and Sin3B) regulate gene expression at the chromatin-level by serving as an anchor onto which the core Sin3/HDAC complex is assembled. The Sin3/HDAC co-repressor complex can be recruited by a large number of DNA-binding transcription factors. Sin3A has been closely linked to p53 while Sin3B is considered to be a close associate of E2Fs. The theme of this study was to establish the role of Sin3B in p53-mediated gene repression. We demonstrate a direct protein-protein interaction between human p53 and Sin3B (hSin3B). Amino acids 1–399 of hSin3B protein are involved in its interaction with N-terminal region (amino acids 1–108) of p53. Genotoxic stress induced by Adriamycin treatment increases the levels of hSin3B that is recruited to the promoters of p53-target genes (HSPA8, MAD1 and CRYZ). More importantly recruitment of hSin3B and repression of the three p53-target promoters upon Adriamycin treatment were observed only in p53+/+ cell lines. Additionally an increased tri-methylation of the H3K9 residue at the promoters of HSPA8 and CRYZ was also observed following Adriamycin treatment. The present study highlights for the first time the essential role of Sin3B as an important associate of p53 in mediating the cellular responses to stress and in the transcriptional repression of genes encoding for heat shock proteins or proteins involved in regulation of cell cycle and apoptosis.

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Section: Discussionsupporting

confidence: 92%

Tumor Suppressor Protein p53 Recruits Human Sin3B/HDAC1 Complex for Down-Regulation of Its Target Promoters in Response to Genotoxic Stress

Bansal

Kadamb²,

Mittal³

et al. 2011

PLoS ONE

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“…45 Moreover, chromatin immunoprecipitation (ChIP) analyses demonstrated specific E2F4 recruitment to the promoter binding sites of PTTG1 and BUB3. In contrast, E2F4 was bound constitutively to Cdc6, an observation similar to the constitutive chromatin binding by p53 to its target promoters, 46 indicating the involvement of other factors or post-transcriptional regulation for their activation. PTTG1, BUB1, BUB3, Mad2, and CENP-E are mitotic checkpoint proteins (Fig.…”

Section: E2f Family Proteins: From Dna Damage To a Stable G 2 Arrestmentioning

confidence: 71%

E2F4 Function in G2 Maintaining G2-arrest to Prevent Mitotic Entry with Damaged DNA

Plesca¹,

Crosby²,

Gupta³

2007

Cell Cycle

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“…It is expected that studies on gene expression at large scale may contribute to clarify the mechanism underlying cellular resistance to radiotherapy. In fact, reports about modulation of gene expression in response to IR in tumor cell lines, such as leukemia, 10 lymphoma, 11 cervical 12 and lung cancer 13 have indicated a list of radiation-responsive genes, but quantitative and qualitative differences have been found among different studies.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional changes in U343 MG-a glioblastoma cell line exposed to ionizing radiation

Bassi

Mello²,

Cardoso³

et al. 2008

Hum Exp Toxicol

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Glioblastoma multiforme (GBM) is a highly invasive and radioresistant brain tumor. Aiming to study how glioma cells respond to γ-rays in terms of biological processes involved in cellular responses, we performed experiments at cellular context and gene expression analysis in U343-MG-a GBM cells irradiated with 1 Gy and collected at 6 h post-irradiation. The survival rate was approximately 61% for 1 Gy and was completely reduced at 16 Gy. By performing the microarray technique, 859 cDNA clones were analyzed. The Significance Analysis of Microarray algorithm indicated 196 significant expressed genes (false discovery rate (FDR) = 0.42%): 67 down-regulated and 97 up-regulated genes, which belong to several classes: metabolism, adhesion/cytoskeleton, signal transduction, cell cycle/apoptosis, membrane transport, DNA repair/DNA damage signaling, transcription factor, intracellular signaling, and RNA processing. Differential expression patterns of five selected genes ( HSPA9B, INPP5A, PIP5K1A, FANCG, and TPP2) observed by the microarray analysis were further confirmed by the quantitative real time RT-PCR method, which demonstrated an up-regulation status of those genes. These results indicate a broad spectrum of biological processes (which may reflect the radio-resistance of U343 cells) that were altered in irradiated glioma cells, so as to guarantee cell survival.

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p53 Binding to Target Sites Is Dynamically Regulated Before and After Ionizing Radiation-Mediated DNA Damage

Cited by 11 publications

References 0 publications

Tumor Suppressor Protein p53 Recruits Human Sin3B/HDAC1 Complex for Down-Regulation of Its Target Promoters in Response to Genotoxic Stress

Tumor Suppressor Protein p53 Recruits Human Sin3B/HDAC1 Complex for Down-Regulation of Its Target Promoters in Response to Genotoxic Stress

E2F4 Function in G2 Maintaining G2-arrest to Prevent Mitotic Entry with Damaged DNA

Transcriptional changes in U343 MG-a glioblastoma cell line exposed to ionizing radiation

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