p53 Down-Regulates ER-Responsive Genes by Interfering with the Binding of ER to ERE

Liu, G.; Schwartz, Janice A.; Brooks, S.C.

doi:10.1006/bbrc.1999.1525

Cited by 48 publications

(30 citation statements)

References 43 publications

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“…In the case of nuclear receptors, p53 binds directly to the transcriptional activator and blocks DNA binding [7][8][9]. We have also previously observed that p53 can repress the transactivation function of HNF4α1 by binding the HNF4α activation domain and recruiting HDAC activity to HNF4α target genes [10].…”

Section: Introductionmentioning

confidence: 89%

Tumour suppressor p53 down-regulates the expression of the human hepatocyte nuclear factor 4α (HNF4α) gene

Maeda

Hwang‐Verslues

Wei

et al. 2006

Biochemical Journal

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The liver is exposed to a wide variety of toxic agents, many of which damage DNA and result in increased levels of the tumour suppressor protein p53. We have previously shown that p53 inhibits the transactivation function of HNF (hepatocyte nuclear factor) 4α1, a nuclear receptor known to be critical for early development and liver differentiation. In the present study we demonstrate that p53 also down-regulates expression of the human HNF4α gene via the proximal P1 promoter. Overexpression of wild-type p53 down-regulated endogenous levels of both HNF4α protein and mRNA in Hep3B cells. This decrease was also observed when HepG2 cells were exposed to UV irradiation or doxorubicin, both of which increased endogenous p53 protein levels. Ectopically expressed p53, but not a mutant p53 defective in DNA binding (R249S), down-regulated HNF4α P1 promoter activity. Chromatin immunoprecipitation also showed that endogenous p53 bound the HNF4α P1 promoter in vivo after doxorubicin treatment. The mechanism by which p53 down-regulates the P1 promoter appears to be multifaceted. The down-regulation was partially recovered by inhibition of HDAC activity and appears to involve the positive regulator HNF6α. p53 bound HNF6α in vivo and in vitro and prevented HNF6α from binding DNA in vitro. p53 also repressed stimulation of the P1 promoter by HNF6α in vivo. However, since the R249S p53 mutant also bound HNF6α, binding HNF6α is apparently not sufficient for the repression. Implications of the p53-mediated repression of HNF4α expression in response to cellular stress are discussed.

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Section: Introductionmentioning

confidence: 89%

Tumour suppressor p53 down-regulates the expression of the human hepatocyte nuclear factor 4α (HNF4α) gene

Maeda

Hwang‐Verslues

Wei

et al. 2006

Biochemical Journal

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“…With respect to Pol II inhibition, several mechanisms have been documented (Figure 3). These include repression of transcription activators by physical interaction with and preventing them from activating the promoter [111][112][113][114][115][116] or by displacing them from the adjusting or overlapping binding sites within the promoter, [117][118][119][120] interference with the assembly of transcription machinery, 7,121 repression through the recruitment of histone deacetylase (HDAC) and, possibly, other chromatin modifying factors, [122][123][124] and finally through novel REs with the unique architecture that dictates the outcome of p53 binding. 14,125 Combination of two of the above mechanisms has been also documented.…”

Section: Transcription Regulation By P53mentioning

confidence: 99%

Transcriptional regulation by p53: one protein, many possibilities

2006

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The p53 tumor suppressor protein is a DNA sequence-specific transcriptional regulator that, in response to various forms of cellular stress, controls the expression of numerous genes involved in cellular outcomes including among others, cell cycle arrest and cell death. Two key features of the p53 protein are required for its transcriptional activities: its ability to recognize and bind specific DNA sequences and to recruit both general and specialized transcriptional co-regulators. In fact, multiple interactions with co-activators and corepressors as well as with the components of the general transcriptional machinery allow p53 to either promote or inhibit transcription of different target genes. This review focuses on some of the salient features of the interactions of p53 with DNA and with factors that regulate transcription. We discuss as well the complexities of the functional domains of p53 with respect to these interactions.

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“…ER has been shown to control p53 mRNA expression [9;10] and vice-versa [11;12]. p53 can also down-regulate ERresponsive genes by interfering with the binding of ER to its response element (RE) [13][14][15], and reciprocally, ER can repress p53 function [16][17][18]. Positive regulation of ER and p53 may also cooperate in the induction of some genes through p53 and ER REhalf-sites located in promoter regions [19].…”

Section: Introductionmentioning

confidence: 99%

Estrogen levels act as a rheostat on p53 levels and modulate p53-dependent responses in breast cancer cell lines

Fernández-Cuesta

Anaganti

Hainaut

et al. 2010

Breast Cancer Res Treat

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p53 Down-Regulates ER-Responsive Genes by Interfering with the Binding of ER to ERE

Cited by 48 publications

References 43 publications

Tumour suppressor p53 down-regulates the expression of the human hepatocyte nuclear factor 4α (HNF4α) gene

Tumour suppressor p53 down-regulates the expression of the human hepatocyte nuclear factor 4α (HNF4α) gene

Transcriptional regulation by p53: one protein, many possibilities

Estrogen levels act as a rheostat on p53 levels and modulate p53-dependent responses in breast cancer cell lines

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