Identification of Tcf-4 as a transcriptional target of p53 signalling

Rother, Karen; Johne, C; Spiesbach, Katja; Haugwitz, Ulrike; Tschöp, Katrin; Wasner, Mark; Klein-Hitpaß, Ludger; Möröy, Tarik; Mössner, Joachim; Engeland, Kurt

doi:10.1038/sj.onc.1207464

Cited by 57 publications

(61 citation statements)

References 68 publications

(82 reference statements)

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“…We found Cks2 mRNA to be downregulated 9.7-fold when wild-type p53 was overexpressed relative to the uninduced state. As controls and consistent with previous observations mRNA levels for known p53 target genes like p21 WAF1/CIP1 and mdm2 were found to be upregulated and previously described targets like cyclin A, Cyclin B, cdk1 and cdc25C were downregulated [25]. Furthermore, under the experimental conditions employed changes in expression of p53 target genes precede the changes due to impending apoptosis [17].…”

Section: Resultssupporting

confidence: 90%

“…Binding of p53 to the p21 WAF1/CIP1 promoter served as a positive control. Taken together, sequence and ChIP analyses indicate that p53 does not bind to the Cks2 promoter as also observed with other genes repressed by p53 [25].…”

Section: Repression Of Cks2 Transcription Appears To Be Independentsupporting

confidence: 78%

“…In control experiments we had confirmed that after tet-off induction for 9 h expression of p53 mRNA and protein increases [8]. To search for hitherto unidentified p53 target genes, we had performed a DNA microarray hybridization experiment using RNA from these DLD-1-tet-off-p53 cells without and 9 h after induction of p53 expression [25]. We found Cks2 mRNA to be downregulated 9.7-fold when wild-type p53 was overexpressed relative to the uninduced state.…”

Section: Resultsmentioning

confidence: 99%

“…Goat-anti-mouse IgG conjugated with horseradish peroxidase (Pierce) was used as a secondary antibody and chemiluminescent signals were detected by Supersignal Ò West Dura Extended Duration Chemiluminescent Substrate Kit (Pierce). Oligonucleotide microarray analysis was performed as described previously [25].…”

Section: Western Blotting and Oligonucleotide Microarray Analysismentioning

confidence: 99%

“…EF026653). Primers for amplification of the human p21 WAF1/CIP1 promoter fragment have been described [25].…”

Section: Chromatin Immunoprecipitation Assaysmentioning

confidence: 99%

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Gene expression of cyclin‐dependent kinase subunit Cks2 is repressed by the tumor suppressor p53 but not by the related proteins p63 or p73

Rother¹,

Dengl²,

Lorenz³

et al. 2007

FEBS Letters

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Cks2 proteins are essential components of cyclin/cyclin-dependent kinase complexes and contribute to cell cycle control. We identify Cks2 as a transcriptional target downregulated by the tumor suppressor p53. Cks2 expression was found to be repressed by p53 both at the mRNA and the protein levels. p53 downregulates transcription from the Cks2 promoter in a dosedependent manner and in all cell types tested. This repression appears to be independent of p53 binding to the Cks2 promoter. In contrast to p53, neither p63 nor p73 proteins can repress Cks2 transcription. Thus p53, rather than its homologues p63 and p73, may contribute to control of the first metaphase/anaphase transition of mammalian meiosis by downregulation of Cks2 expression.

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Section: Resultssupporting

confidence: 90%

Section: Repression Of Cks2 Transcription Appears To Be Independentsupporting

confidence: 78%

Section: Resultsmentioning

confidence: 99%

Section: Western Blotting and Oligonucleotide Microarray Analysismentioning

confidence: 99%

“…EF026653). Primers for amplification of the human p21 WAF1/CIP1 promoter fragment have been described [25].…”

Section: Chromatin Immunoprecipitation Assaysmentioning

confidence: 99%

See 3 more Smart Citations

Gene expression of cyclin‐dependent kinase subunit Cks2 is repressed by the tumor suppressor p53 but not by the related proteins p63 or p73

Rother¹,

Dengl²,

Lorenz³

et al. 2007

FEBS Letters

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A 3D Cell Culture Model Identifies Wnt/β‐Catenin Mediated Inhibition of p53 as a Critical Step during Human Hepatocyte Regeneration

et al. 2020

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The liver is a highly regenerative organ. While mature hepatocytes under homeostatic conditions are largely quiescent, upon injury, they rapidly enter the cell cycle to recover the damaged tissue. In rodents, a variety of injury models have provided important insights into the molecular underpinnings that govern the proliferative activation of quiescent hepatocytes. However, little is known about the molecular mechanisms of human hepatocyte regeneration and experimental methods to expand primary human hepatocytes (PHH). Here, a 3D spheroid model of PHH is established to study hepatocyte regeneration and integrative time‐lapse multi‐omics analyses show that upon isolation from the native liver PHH acquire a regenerative phenotype, as seen in vivo upon partial hepatectomy. However, proliferation is limited. By analyzing global promoter motif activities, it is predicted that activation of Wnt/ β ‐catenin and inhibition of p53 signaling are critical factors required for human hepatocyte proliferation. Functional validations reveal that activation of Wnt signaling through external cues alone is sufficient to inhibit p53 and its proliferative senescence‐inducing target PAI1 (SERPINE1) and drive proliferation of >50% of all PHH. A scalable 3D culture model is established to study the molecular and cellular biology of human hepatocyte regeneration. By using this model, an essential role of Wnt/ β ‐catenin signaling during human hepatocyte regeneration is identified.

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The human immunodeficiency virus reduces network capacity: Acoustic noise effect

Tomasi

Chang

Caparelli

et al. 2006

Annals of Neurology

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Increased acoustic noise (AN) during working memory (WM) leads to increased brain activation in healthy individuals, and may have greater impact in human immunodeficiency virus (HIV) patients. Compared to controls, HIV subjects showed reduced AN-activation and lower neuronal marker Nacetylaspartate in prefrontal and parietal cortices. Competing use of the WM network between AN and cognitive load showed lower dynamic range of the hemodynamic responses in prefrontal and parietal cortices in HIV patients. These findings suggest reduced reserve capacity of the WM network in HIV patients and additional stress (e.g. AN) might exhaust the impaired network for more demanding tasks.

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Identification of Tcf-4 as a transcriptional target of p53 signalling

Cited by 57 publications

References 68 publications

Gene expression of cyclin‐dependent kinase subunit Cks2 is repressed by the tumor suppressor p53 but not by the related proteins p63 or p73

Gene expression of cyclin‐dependent kinase subunit Cks2 is repressed by the tumor suppressor p53 but not by the related proteins p63 or p73

A 3D Cell Culture Model Identifies Wnt/β‐Catenin Mediated Inhibition of p53 as a Critical Step during Human Hepatocyte Regeneration

The human immunodeficiency virus reduces network capacity: Acoustic noise effect

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