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 SamplesThis SuperSeries is composed of the SubSeries listed below.
siPools: highly complex but accurately defined siRNA pools eliminate off-target effects.
Cell line
View SamplesShort interfering RNAs (siRNA) are widely used as tool for gene inactivation in basic research and therapeutic applications. One of the major shortcomings of siRNA experiments are sequence-specific Off-target effects. Such effects are largely unpredictable because siRNAs can affect partially complementary sequences and function like microRNAs (miRNAs), which inhibit gene expression on mRNA stability or translational levels.
siPools: highly complex but accurately defined siRNA pools eliminate off-target effects.
Cell line
View Samplessh RNA of p73 in Fibroblasts compared to non-silencing control
p73 poses a barrier to malignant transformation by limiting anchorage-independent growth.
No sample metadata fields
View SamplesTotal, nascent and unlabeled RNA were prepared following 1h of labeling with 100 M 4-thiouridine and 3 replicates analyzed by Affymetrix Gene ST 1.0 arrays
Systematic analysis of viral and cellular microRNA targets in cells latently infected with human gamma-herpesviruses by RISC immunoprecipitation assay.
Cell line
View SamplesRIP-Chip was performed on DG75-eGFP, DG75-10/12, BCBL-1, BL41, BL41 B95.8 and Jijoye using anti-human Ago2 (11A9) antibodies. Anti-BrdU antibodies were used as controls for DG75-eGFP, DG75-10/12 and BCBL-1. Total RNA was used as control for BL41, BL41 B95.8 and Jijoye. Samples were analyzed on Affymetrix Gene ST 1.0 Arrays (2 independent biological replicates / sample)
Systematic analysis of viral and cellular microRNA targets in cells latently infected with human gamma-herpesviruses by RISC immunoprecipitation assay.
No sample metadata fields
View SamplesSupT1, PBMC, or IMR90 cells were infected with an HIV-based vector (see Schroder et al., Cell 110:521-9) and the RNA isolated 48 hours after infection.
Retroviral DNA integration: ASLV, HIV, and MLV show distinct target site preferences.
No sample metadata fields
View SamplesRift Valley fever virus (RVFV) causes major outbreaks among livestock, characterized by “abortion storms” in which spontaneous abortion occurs in almost 100% of pregnant ruminants. Humans can also become infected with mild symptoms that can progress to more severe symptoms, such as hepatitis, encephalitis, and hemorrhagic fever. The goal of this study was to use RNA-sequencing (RNA-seq) to analyze the host transcriptome in response to RVFV infection. G2/M DNA damage checkpoint, ATM signaling, mitochondrial dysfunction, regulation of the antiviral response, and integrin-linked kinase (ILK) signaling were among the top altered canonical pathways with both the attenuated MP12 strain and the fully virulent ZH548 strain. Although several mRNA transcripts were highly upregulated, an increase at the protein level was not observed for the selected genes, which was at least partially due to the NSs dependent block in mRNA export. Inhibition of ILK signaling, which is involved in cell motility and cytoskeletal reorganization, resulted in reduced RVFV replication, indicating that this pathway is important for viral replication. Overall, this is the first global transcriptomic analysis of the human host response following RVFV infection, which could give insight into novel host responses that have not yet been explored. Overall design: The study included triplicate samples of HSAEC cells infected with Mock, MP12, or ZH548 strains of RVFV, and collected at 3, 9, and 18 hourse post-infection. There are a total of 27 samples.
Phosphoproteomic analysis reveals Smad protein family activation following Rift Valley fever virus infection.
Specimen part, Subject, Time
View SamplesThe in vitro effect of infection with different strains of Toxoplasma gondii was tested 24 hours after infection of Human Foreskin Fibroblasts (HFF)
Integrative genomic approaches highlight a family of parasite-specific kinases that regulate host responses.
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Differential induction of TLR3-dependent innate immune signaling by closely related parasite species.
Specimen part, Cell line
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