PXD001976-4

PXD001976 is an original dataset announced via ProteomeXchange.

Title	p53-regulated networks of protein, mRNA, miRNA and lncRNA expression revealed by integrated pSILAC and NGS analyses
Description	We determined the effect of p53 activation on de novo protein synthesis using quantitative proteomics of newly synthesized proteins (pulsed stable isotope labeling with amino acids in cell culture, pSILAC) in combination with mRNA and non-coding RNA expression analyses by next generation sequencing (RNA-, miR-Seq) in the colorectal cancer (CRC) cell line SW480. Furthermore, genome-wide DNA binding of p53 was analyzed by chromatin-immunoprecipitation (ChIP-Seq). Thereby, we identified differentially regulated mRNAs (1258 up, 415 down), miRNAs (111 up, 95 down), lncRNAs (270 up, 123 down) and proteins (542 up, 569 down). Changes in mRNA and protein expression levels showed a positive correlation (r = 0.50, p < 0.0001). More transcriptionally induced genes displayed occupied p53 binding sites (4.3% mRNAs, 7.2% miRNAs, 6.3% lncRNAs, 5.9% proteins) than repressed genes (2.4% mRNAs, 3.2% miRNAs, 0.8% lncRNAs, 1.9% proteins), suggesting indirect mechanisms of repression. Around 50% of the downregulated proteins displayed seed-matching sequences of p53-induced miRNAs in the corresponding 3’-UTRs. Moreover, proteins repressed by p53 significantly overlapped with those previously shown to be repressed by miR-34a. We confirmed upregulation of the novel direct p53 target genes LINC01021, MDFI, ST14 and miR-486 and showed that ectopic LINC01021 expression inhibited proliferation in SW480 cells. Furthermore, HMGB1, KLF12 and CIT mRNAs were confirmed as direct targets of the p53-induced miR-34a, miR-205 and miR-486-5p, respectively. In line with the loss of p53 function during tumor progression, elevated expression of HMGB1, KLF12 and CIT was detected in advanced stages of cancer. This study provides new insights and a comprehensive catalogue of p53-mediated regulations and p53 DNA binding in CRC cells.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:23:15.602.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Friedel Drepper
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	6x(13)C; 6x(13)C; (4,4,5,5-(2)H4)-L-lysine; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue; 6x(13)C labeled L-arginine
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2015-03-25 02:21:55	ID requested
1	2015-07-23 05:28:18	announced
2	2015-07-24 01:57:09	announced	Updated project metadata.
3	2015-07-24 04:18:58	announced	Updated project metadata.
⏵ 4	2024-10-22 04:23:20	announced	2024-10-22: Updated project metadata.

H, ü, nten S, Kaller M, Drepper F, Oeljeklaus S, Bonfert T, Erhard F, Dueck A, Eichner N, Friedel CC, Meister G, Zimmer R, Warscheid B, Hermeking H, p53-Regulated Networks of Protein, mRNA, miRNA, and lncRNA Expression Revealed by Integrated Pulsed Stable Isotope Labeling With Amino Acids in Cell Culture (pSILAC) and Next Generation Sequencing (NGS) Analyses. Mol Cell Proteomics, 14(10):2609-29(2015) [pubmed]

curator keyword: Biomedical

submitter keyword: pSILAC, Human, transcriptional network, biomarker,p53, tumor-suppressor

Bettina Warscheid
contact affiliation	Functional Proteomics Lab, Faculty of Biology, University of Freiburg, Germany
contact email	bettina.warscheid@biologie.uni-freiburg.de
lab head
Friedel Drepper
contact affiliation	AG Warscheid Biologie II Albert-Ludwigs-Universität Freiburg Schänzlestr. 1 79104 Freiburg Germany
contact email	friedel.drepper@biologie.uni-freiburg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD001976
     1. Label: PRIDE project
     2. Name: p53-regulated networks of protein, mRNA, miRNA and lncRNA expression revealed by integrated pSILAC and NGS analyses