The p53 family is known as a family of transcription factors with functions in tumor suppression and development. Whereas the central DNA binding domain is highly conserved among the three family members p53, p63 and p73, the C-terminal domains (CTDs) are diverse and subject to alternative splicing and post-translational modification. Here we demonstrate that the CTDs strongly influence DNA binding and transcriptional activity. While p53 and the p73 isoform p73gamma have basic CTDs and form weak sequence-specific protein-DNA complexes, the major p73 isoforms alpha, beta and delta have neutral CTDs and bind DNA strongly. A basic CTD has been previously shown to enable sliding along the DNA backbone and to facilitate the search for binding sites in the complex genome. Our experiments, however, reveal that a basic CTD also reduces protein-DNA complex stability, intranuclear mobility, promoter occupancy in vivo, transgene activation and induction of cell cycle arrest or apoptosis. A basic CTD in p53 and p73gamma therefore provides both positive and negative regulatory functions presumably to enable rapid switching of protein activity in response to stress. In contrast, most p73 isoforms exhibit constitutive DNA binding activity consistent with a predominant role in developmental control.
C-terminal diversity within the p53 family accounts for differences in DNA binding and transcriptional activity.
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View Samplessh RNA of p73 in Fibroblasts compared to non-silencing control
p73 poses a barrier to malignant transformation by limiting anchorage-independent growth.
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View SamplesRibosome Profiling was employed to learn about Ribosome A-site occupancies in response to uL11 siRNA treatment or scrambled siRNA treatment in Cystic Fibrosis Bronchial Epithelial (CFBE) cells. Overall design: Ribosome Profiling of cells 96h after siRNA transfection
Slowing ribosome velocity restores folding and function of mutant CFTR.
Specimen part, Subject
View SamplesWe investigated whether we could identify gene expression profiles in initial core biopsies of breast cancer samples that would permit to a) predict a clinically meaningful response to Epi/Doc in terms of tumor size reduction, b) predict a profound reduction in intratumoral Ki67 protein expression, and c) predict an in vitro response to Epi/Doc in the ATP-TCA.
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Specimen part
View SamplesUsing these samples, it has been shown that the transcriptional landscape in glomeruli of Ercc1[-/] mice at a rather young age of 14 weeks mimics that of mice which have undergone real-life renal aging. Thus, young Ercc1[-/] mice can be used as a model system for glomerular aging in future studies.
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Age
View SamplesIschemia reperfusion injury (IRI) in organ transplantation remains a significant problem with limited alternative therapeutic options. Organs that undergo significant damage during IRI, particularly those enduring long warm ischemia times, undergo significant delayed graft function (DGF) after reperfusion and tend to have greater complications long term with the onset of chronic rejection. The gas molecule carbon monoxide (CO) has emerged as an agent that can suppress IRI in rodent models of solid organ transplantation. Since the use of CO is a potential therapeutic modality in humans, we tested if CO can prevent DGF in a pig model of kidney transplantation
Intraoperative administration of inhaled carbon monoxide reduces delayed graft function in kidney allografts in Swine.
Specimen part
View SamplesRegulation of genes in shoots and roots and Arabidopsis in response to Zn-deficiency in wild-type and hma2 hma4 mutants plants
Systemic Upregulation of MTP2- and HMA2-Mediated Zn Partitioning to the Shoot Supplements Local Zn Deficiency Responses.
Age, Specimen part
View SamplesThe transition between growth in the dark (skotomorphogenesis) and growth in the light (photomorphogenesis) is one of the most critical in plant development. Here the newly identified mutant dez is photomorphogenic in the dark and is strongly enhanced in high Zn. dez displays a shortened hypocotyl, expanded cotyledons, an elongated root and differentiated plastids in the dark contrast to wild-type seedlings that are typically skotomorphogenic, with a long hypocotyl and unexpanded cotyledons protected by an apical hook, and undifferentiated etioplasts
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Specimen part
View SamplesThe anaerobic metabolism of the opportunistic pathogen Pseudomonas aeruginosa is important for growth and survival during persistent infections. The two Fnr-type transcription factors Anr and Dnr regulate different parts of the underlying network. Both are proposed to bind to a non-distinguishable DNA sequence named Anr box.
Anaerobic adaptation in Pseudomonas aeruginosa: definition of the Anr and Dnr regulons.
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View SamplesTyrosine kinase inhibitors represent a new generation of targeted drugs for cancer treatment and chemoprevention. The EGF receptor inhibitor erlotinib is under discussion for chemoprevention of hepatocellular carcinoma.
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Specimen part, Cell line
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