Whole-genome cartography of p53 response elements ranked on transactivation potential

Tebaldi, Toma; Zaccara, Sara; Alessandrini, Federica; Bisio, Alessandra; Ciribilli, Yari; Inga, Alberto

doi:10.1186/s12864-015-1643-9

Cited by 59 publications

(63 citation statements)

References 66 publications

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“…It is well-acknowledged that p53 transactivates its target genes through binding to a consensus RE (39)(40)(41)(42)(43)(44). However, the mechanism by which p53 elicits cell-type specific responses is not fully understood.…”

Section: Discussionmentioning

confidence: 99%

p53 positively regulates the expression of cancer stem cell marker CD133 in HCT116 colon cancer cells

et al. 2018

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Abstract. Colon cancer stem cells (CSCs), which are highly capable of self-renewal and proliferation, are involved in colon tumorigenesis and response to therapy. CD133 is considered the most robust surface marker for colorectal cancer stem cells. Although the TP53 gene is frequently mutated in colon cancer, it remains not fully understood whether and how tumor protein p53 (p53) is associated with CD133 expression in colon cancer cells. In the present study, the expression of the CSC biomarker CD133 was investigated in terms of p53 status in colorectal carcinoma HCT116 cells. p53 wild-type HCT116 (HCT116 p53 IntroductionColorectal carcinoma (CRC), which is prone to metastasis and recurrence, is a cancer with a high lethality rate worldwide. More than 50% of patients will develop metastasis and recurrence (1,2). Multiple factors account for metastasis and recurrence, including tumor stage, cancer subtypes and cancer stem cells (CSCs). CSCs are a small population of tumor-initiating cells that have the ability to self-renew and differentiate in tumors in vivo. CSCs are involved in various processes during tumor formation, progression, and angiogenesis and are considered an important target for novel cancer treatment strategies (3). Several specific surface markers are expressed on CSCs, including CD133, CD44 and aldehyde dehydrogenase 1 (ALDH1) (4). CD133 (also known as prominin-1) is a 5-transmembrane glycoprotein of 865 amino acids with a total molecular weight of 120 kDa. CD133 is a CSC marker in colon carcinoma. CD133-positive cells correlate strongly with poor prognosis and synchronous liver metastasis (5). Cancer cell populations with high expression of CD133 are much more aggressive in terms of metastases compared with those with low expression of CD133, suggesting that CD133 may be a marker of increased tumorigenesis ability. CD133-positive cells from clinical biopsy-derived cultures have been demonstrated to possess multilineage differentiation potential and are capable of tumor initiation in vivo. CD133-positive CRC cells are more resistant to chemoradiotherapy, and CD133 expression is associated with poor prognosis (6,7). However, the regulation of CD133 expression has not been fully elucidated.The present study demonstrated that CD133 expression was associated with the tumor protein p53 (p53) expression in an HCT116 p53 +/+ cell line. Of note, CD133-negative cells were detected in the colon cancer cell line HCT116 in a previous report by Kai et al (8

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Section: Discussionmentioning

confidence: 99%

p53 positively regulates the expression of cancer stem cell marker CD133 in HCT116 colon cancer cells

et al. 2018

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“…Table 1). From this, it could be deduced that p53 REs are indeed enriched on 105 out of 119 genes (74 RP and 31 EIF genes) as detected by p53 retriever [20] and that p53 binds to at least 76 genes (51 RP and 25 EIF genes). Many RP and eIF genes, in which REs were detected by using p53famtag and p53 retriever, bind p53 in ChIP-seq data (Suppl.…”

Section: Data From P53famtagmentioning

confidence: 99%

“…Therefore, for a convenient understanding of the data used in the present study, either the TAp63α or ΔNp63α overexpression is referred to as p63, whereas either the TAp73α or TAp73β expression is referred to as p73. However, a detailed data corresponding to each p53 family member overexpressing conditions obtained for the present study from p53famtag database is listed in supplementary table 1. p53 retriever detected RE data The p53 retriever detected RE data was collated from a recently published study of whole genome cartography of p53 REs [20]. Enrichment of REs on the RP and EIF genes used for the query in the p53famtag were again checked with the data listed in this recent study.…”

Section: Additional Informationmentioning

confidence: 99%

“…The p53 retriever detected RE data was collated from a recently published study of whole genome cartography of p53 REs [20]. Enrichment of REs on the RP and EIF genes used for the query in the p53famtag were again checked with the data listed in this recent study.…”

Section: Data From P53famtagmentioning

confidence: 99%

“…To verify the reliability of this data, it was compared with two separate datasets, the REs detected by another tool, known as p53 retriever [20], and a p53 ChIP-seq data [21] (Fig. 1F representing the data from Suppl.…”

Section: Data From P53famtagmentioning

confidence: 99%

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In silico analysis reveals p53 responsive ribosomal protein and eukaryotic translation initiation factor genes: a route for p53 to influence ribosome assembly and translation

Yadav

2016

Matters

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The ribosome is the protein synthesis machinery of cells, which provides them with essential proteins. An increase in ribosomal content and protein synthesis is evidenced in cancers, most notably in cancers with a loss of p53. However, very little is known as to how the p53 or its family influences the ribosome and translation. Interestingly, in this study, a large number of genes encoding ribosomal proteins (RP) and eukaryotic initiation factors (eIFs) that are intrinsic to ribosome assembly and translation initiation, respectively, were found to possess p53 responsive elements (REs) in their regulatory region. To understand whether p53 or its family influences the ribosome, the expression patterns of the RE-containing RP and EIF genes were examined in a p53 family target microarray database. Many RP and EIF gene expressions were found to be deregulated during the p53 or its family gene overexpression. These results indicate that ribosome assembly and its functions respond to p53 activity. The overall influence of p53 was found to be repressive on RP and EIF gene expression, which led the author to hypothesize that p53 controls the formation of ribosomes and the translation of mRNA into proteins. The study brings to light a regulatory pathway through which the p53 family influences the ribosome with great implications on the cell fate. IntroductionRibosomes are central to cellular processes because of their role in translating mRNA into proteins. The assembly of the ribosome from several ribosomal proteins (RPs) and ribosomal RNAs (rRNA) and its subsequent association with eukaryotic initiation factors (eIFs) and mRNA is a prerequisite for translation [1]. A balanced production of RPs, rRNAs and eIFs influences translation [2] [3] and determines cell fate [4] [5]. Hence, it is important to know how the transcription of ribosomal and translational genes is regulated to ensure sufficient levels of RPs and eIFs for the assembly and function of ribosomes respectively. In some cancers, the loss of p53 is correlated with an increase in ribosomal content and translation, which suggests that accelerated protein synthesis is a major contributor to oncogenesis during p53 loss [6] [7] [8] [9] [10]. Recently, an experimental knockdown of p53 in zebrafish embryos increased the ribosomal content, but the mechanism through which this is achieved is yet to be known [11]. The transcription factor p53 controls the expression of an exhaustive list of target genes, which are involved in cell cycle arrest and apoptosis, and thus acts as a tumor suppressor that regulates cell proliferation [12] [13]. On the other hand, the p53 family genes (p63 and p73) are known for their role in transcription of genes involved in development and differentiation [14]. The transcriptional targets of p53 family have responsive elements (REs), which are consensus sequences of nucleotides that are usually distributed on promoter or intronic regions. In its tetrameric form, the p53 binds to REs on target genes and influences their transcription....

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Effect of p53 and its N‐terminally truncated isoform, Δ40p53, on breast cancer migration and invasion

et al. 2021

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Breast cancer is the most diagnosed malignancy in women, with over half a million women dying from this disease each year. In our previous studies, ∆40p53, an N‐terminally truncated p53 isoform, was found to be upregulated in breast cancers, and a high ∆40p53 : p53α ratio was linked with worse disease‐free survival. Although p53α inhibits cancer migration and invasion, little is known about the role of ∆40p53 in regulating these metastasis‐related processes and its role in contributing to worse prognosis. The aim of this study was to assess the role of ∆40p53 in breast cancer migration and invasion. A relationship between Δ40p53 and gene expression profiles was identified in oestrogen‐receptor‐positive breast cancer specimens. To further evaluate the role of Δ40p53 in oestrogen‐receptor‐positive breast cancer, MCF‐7 and ZR75‐1 cell lines were transduced to knockdown p53α or Δ40p53 and overexpress Δ40p53. Proliferation, migration and invasion were assessed in the transduced sublines, and gene expression was assessed through RNA‐sequencing and validated by reverse‐transcription quantitative PCR. Knockdown of both p53α and ∆40p53 resulted in increased proliferation, whereas overexpression of ∆40p53 reduced proliferation rates. p53α knockdown was also associated with increased cell mobility. ∆40p53 overexpression reduced both migratory and invasive properties of the transduced cells. Phenotypic findings are supported by gene expression data, including differential expression of LRG1, HYOU1, UBE2QL1, SERPINA5 and PCDH7. Taken together, these results suggest that, at the basal level, ∆40p53 works similarly to p53α in suppressing cellular mobility and proliferation, although the role of Δ40p53 may be cell context‐specific.

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Whole-genome cartography of p53 response elements ranked on transactivation potential

Cited by 59 publications

References 66 publications

p53 positively regulates the expression of cancer stem cell marker CD133 in HCT116 colon cancer cells

p53 positively regulates the expression of cancer stem cell marker CD133 in HCT116 colon cancer cells

In silico analysis reveals p53 responsive ribosomal protein and eukaryotic translation initiation factor genes: a route for p53 to influence ribosome assembly and translation

Effect of p53 and its N‐terminally truncated isoform, Δ40p53, on breast cancer migration and invasion

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Whole-genome cartography of p53 response elements ranked on transactivation potential

Cited by 59 publications

References 66 publications

p53 positively regulates the expression of cancer stem cell marker CD133 in HCT116 colon cancer cells

p53 positively regulates the expression of cancer stem cell marker CD133 in HCT116 colon cancer cells

In silico&nbsp;analysis reveals p53 responsive ribosomal protein and eukaryotic translation initiation factor genes: a route for p53 to influence ribosome assembly and translation

Effect of p53 and its N‐terminally truncated isoform, Δ40p53, on breast cancer migration and invasion

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In silico analysis reveals p53 responsive ribosomal protein and eukaryotic translation initiation factor genes: a route for p53 to influence ribosome assembly and translation