Unknown,Transcriptomics,Genomics,Proteomics

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The codon 72 polymorphism of p53 regulates interactions with NF-κB and transactivation of genes involoved in immunity and inflamation

ABSTRACT: A common polymorphism at codon 72 in the p53 tumor suppressor gene encodes either proline(P72) or arginine(R72). These two variants might possess altered biological function which influences p53’s transcriptional, senescence and apoptotic functions. We found that P72 has increased apoptosis when compare to R72. To further identify unknown p53 target genes which might play a role in the increased apoptosis in P72 thymocytes, we have employed whole genome microarray expression profiling as a discovery platform. Mouse thymocytes were isolated from the thymuses of mice that were untreated (0 hour) or following 2 or 4 hours of exposure to 5 Gray of gamma radiation. Mouse thymocytes were isolated from the thymuses of mice that were untreated (0 hour) or following 2 or 4 hours of exposure to 5 Gray of gamma radiation. Four independent experiments were performed at each time point (P72 and R72) and at each timepoint 2 mice of each genotype were used, and their thymocytes were pooled together.

ORGANISM(S): Mus musculus

SUBMITTER: Maureen Murphy

PROVIDER: E-GEOD-26851 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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The codon 72 polymorphism of p53 regulates interaction with NF-{kappa}B and transactivation of genes involved in immunity and inflammation.

Frank Amanda K AK Leu Julia I-Ju JI Zhou Yan Y Devarajan Karthik K Nedelko Tatiana T Klein-Szanto Andres A Hollstein Monica M Murphy Maureen E ME

Molecular and cellular biology 20110118 6

A common polymorphism at codon 72 in the p53 tumor suppressor gene encodes either proline (P72) or arginine (R72). Several groups have reported that in cultured cells, this polymorphism influences p53's transcriptional, senescence, and apoptotic functions. However, the impact of this polymorphism within the context of a living organism is poorly understood. We generated knock-in mice with the P72 and R72 variants and analyzed the tissues of these mice for apoptosis and transcription. In the thym ...[more]

PMID: 21245379

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Project description:CD5 is characterized as an inhibitory co-receptor with important regulatory role during T cell development. To study the molecular mechanism by which CD5 operates, we used quantitative mass spectrometry to analyze the components of the CD5 signaling machinery in primary T cells. In a first set of experiments, CD5-containing complexes were immunoprecipitated from thymocytes of wild-type (WT) C57BL/6 mice. Thymocytes were treated with pervanadate to induce widespread activation of protein tyrosine kinases. Corresponding samples prepared from thymocytes of Cd5−/− mice were used as controls, to discriminate CD5-binding molecules from the background of contaminant proteins. Eight biological replicates were prepared for both conditions, and samples were analyzed in duplicate LC-MS runs. This first set of experiment is presented in TableS1 of the paper, and is associated to the MaxQuant result file “Interactome WT” in the present PX dataset. We analyzed the CD5 interactome at different time of stimulation with pervanadate (1min and 10min) using thymocytes from wild-type (WT) C57BL/6 mice. Corresponding samples prepared from thymocytes of Cd5−/− mice were used as controls. Three biological replicates were prepared for both conditions (WT and KO) and each time point (1min and 10min). This set of experiments is presented in TableS2 of the paper and is associated to the MaxQuant result file “Interactome at 1min and 10min” in the present PX dataset. We checked that the activation of CD5 (phosphorylation sites) and the formation of the signaling complex was comparable in different stimulatory conditions (comparison of WT thymocytes stimulated with either pervanadate or anti-CD3+anti-CD4 antibodies). We also analyzed the binding of CD5 interactors in thymocytes from a c-Cbl-/- mouse model (comparison of WT and c-Cbl-/-thymocytes stimulated with pervanadate). These experiments and the associated experimental design of the comparisons are summarized in TableS3 of the paper, and are based on the MaxQuant result file “Comparison of different stimulatory conditions” in this dataset. To check the phosphorylation status of the CD5 tyrosine residues at different time of stimulation, we analyzed samples immunoprecipitated from thymocytes of wild-type (WT) C57BL/6 mice, following stimulation with anti-CD3+anti-CD4 antibodies for 1min, 3min and 10min. This set of experiment is presented in TableS4 of the paper and is associated to the MaxQuant result file “CD5 pY kinetics” in the present PX dataset. To determine the role of Y429 in the context of CD5 signaling, we expressed a wild-type (CD5tgWt) or a mutated form of CD5, containing a tyrosine to phenylalanine substitution at position 429 (CD5tgY429F) in transgenic mice. We analyzed the CD5 interactome by comparing samples immunoprecipitated from thymocytes of these 2 mice models (following pervanadate stimulation, 6 and 5 biological replicates respectively) with samples prepared in the same way from Cd5−/− mice as controls (6 biological replicates). The results are shown in TableS5 of the paper, and correspond to the MaxQuant result file “interactome CD5tgWt_CD5tgY429F”.

Dataset Information

The codon 72 polymorphism of p53 regulates interactions with NF-κB and transactivation of genes involoved in immunity and inflamation

Publications

The codon 72 polymorphism of p53 regulates interaction with NF-{kappa}B and transactivation of genes involved in immunity and inflammation.

Similar Datasets

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