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Phosphoproteome of RA-responsive and RA-resistant breast cancer cell lines

ABSTRACT: Retinoic acid (RA), the main active vitamin A metabolite, controls multiple biological processes such as cell proliferation and differentiation through genomic programs and kinase cascades activation. Due to these properties, RA has proven anti-cancer capacity. Several breast cancer cells respond to the antiproliferative effects of RA, while others are RA-resistant. However, the overall signaling and transcriptional pathways that are altered in such cells have not been elucidated. Here, in a large-scale analysis of the phosphoproteins and in a genome-wide analysis of the RA-regulated genes, we compared two human breast cancer cell lines, a RA-responsive one, the MCF7 cell line, and a RA-resistant one, the BT474 cell line, which depicts several alterations of the "kinome".

OTHER RELATED OMICS DATASETS IN: PRJNA322613

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

DISEASE(S): Breast Cancer

SUBMITTER: Luc Negroni

LAB HEAD: Cecile Rochette-Egly

PROVIDER: PXD005911 | Pride | 2020-10-15

REPOSITORIES: Pride

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Publications

Phosphoproteome and Transcriptome of RA-Responsive and RA-Resistant Breast Cancer Cell Lines.

Carrier Marilyn M Joint Mathilde M Lutzing Régis R Page Adeline A Rochette-Egly Cécile C

PloS one 20160630 6

Retinoic acid (RA), the main active vitamin A metabolite, controls multiple biological processes such as cell proliferation and differentiation through genomic programs and kinase cascades activation. Due to these properties, RA has proven anti-cancer capacity. Several breast cancer cells respond to the antiproliferative effects of RA, while others are RA-resistant. However, the overall signaling and transcriptional pathways that are altered in such cells have not been elucidated. Here, in a lar ...[more]

PMID: 27362937

Similar Datasets

Phosphoproteome of RA-responsive and RA-resistant breast cancer cell lines

Project description:Retinoic acid (RA), the main active vitamin A metabolite, controls multiple biological processes such as cell proliferation and differentiation through genomic programs and kinase cascades activation. Due to these properties, RA has proven anti-cancer capacity. Several breast cancer cells respond to the antiproliferative effects of RA, while others are RA-resistant. However, the overall signaling and transcriptional pathways that are altered in such cells have not been elucidated. Here, in a large-scale analysis of the phosphoproteins and in a genome-wide analysis of the RA-regulated genes, we compared two human breast cancer cell lines, a RA-responsive one, the MCF7 cell line, and a RA-resistant one, the BT474 cell line, which depicts several alterations of the "kinome".

2016-07-05 | PXD004357 | Pride

Tousled-like kinases phosphorylate Asf1 to promote histone supply during DNA replication

Project description:During DNA replication, nucleosomes are rapidly assembled on newly synthesized DNA to restore chromatin organization. Asf1, a key histone H3-H4 chaperone required for this process, is phosphorylated by Tousled-Like Kinases (TLKs). Here, we identify TLK phosphorylation sites by mass spectrometry and dissect how phosphorylation impacts on human Asf1 function. The divergent C-terminal tail of Asf1a is phosphorylated at several sites and this is required for timely progression through S phase. Consistent with this, biochemical analysis of wild-type and phospho-mimetic Asf1a shows that phosphorylation enhances binding to histones and the downstream chaperones CAF-1 and HIRA. Moreover, we find that TLK phosphorylation of Asf1a is induced in cells experiencing deficiency of new histones and that TLK interaction with Asf1a involves its histone-binding pocket. We thus propose that TLK signaling promotes histone supply in S phase by targeting histone-free Asf1 and stimulating its ability to shuttle histones to sites of chromatin assembly.

2014-03-06 | PXD000686 | Pride

Proteomic characterization of calcium macrophages

Project description:In this study, macrophages, which differentiated from monocytes due to exposure to calcium and no further growth factors, were characterized. For this purpose, their proteomic profile was compared to monocytes, M1 macrophages, M2 macrophages, DCs, and foam cells obtained from healthy donors or patients with rheumatoid arthritis (RA).

2022-02-17 | PXD026888 | Pride

Structured elements drive circular RNA translation and expand the human proteome, part4

Project description:The human genome encodes tens of thousands circular RNAs (circRNAs) whose levels correlate with many disease states. While studies have focused on the non-coding functions of circRNAs, emerging evidence suggests that a handful of circRNAs encode proteins. Translation canonically starts by recognition of mRNA 5’cap and scanning to the start codon; how circRNA translation initiates remains unclear. Here, we developed a high-throughput screen to systematically identify and quantify RNA sequences that can direct circRNA translation. We identify and validate over 17,000 circRNA internal ribosome entry sites (IRES) and reveal that 18S rRNA complementarity and a structured RNA element on the IRES are important for facilitating circRNA cap-independent translation. With genomic and peptidomic analyses of the IRES, we identified nearly 1,000 putative endogenous protein-coding circRNAs and hundreds of translational units encoded by these circRNAs. We further characterized circFGFR1p, a protein encoded by circFGFR1, functions as a negative regulator of FGFR1 to suppress cell growth under stress conditions. The circRNA proteome may be important links among circRNA, biological control, and disease.

2021-08-26 | PXD025203 | Pride

Proteomic profiling of colorectal cancer cell culture samples treated with apoptosis- and mTOR inhibitors under normoxia and hypoxia

Project description:To examine changes in tyrosine kinase activity in colorectal cancer cell culture samples treated with apoptosis inhibitors or/and mTOR inhibitors, under normoxic or/and hypoxic experimental conditions.

2016-06-15 | E-MTAB-3870 | biostudies-arrayexpress

Genome-wide gene expression to dibenzofuran in Sphingomonas wittichii RW1

Project description:Sphingomonas wittichii RW1 is a bacterium isolated for its ability to degrade the toxic polyaromatic hydrocarbon dibenzofuran (dbf) and its polychlorinated derivatives. Its genome consists of a chromosome and two plasmids, encoding for more than 5300 genes. We studied genome-wide expression of strain RW1 to dbf in three different experimental setups, including both batch cultures and chemostats, comparing in all cases to the transcriptome of cells grown on phenylalanine as carbon source. A short exposure to DBF in chemostat or in batch, provoked the up-regulation of the ECF sigma 24, catalases, peroxiredoxins, chaperones, an aquaporin, several OmpA domain-containing proteins and the down-regulation of genes involved in TCA cycle, oxidative phosphorylation, amino acid metabolism and ribosomal proteins. When growing strain RW1 on DBF, genes known to be involved in DBF degradation were induced 2 to 4 fold. Additionally, two cluster of genes, putatively participating in the gentisate and meta-cleavage branches of the DBF degradation pathway, were induced from 12 to 19 fold. Three experiments are summarized here. 1. Compares the response of exponentially growing S.wittichii RW1 cells on phenylalanine (Phe), washed and resuspended in Phe for 30 min, with that of cells resuspended in DBF medium for 30 min (Phe1_shock, DBF1_schock, etc.). 2. Compares response of RW1 cells grown in batch medium with Phe or DBF as sole carbon and energy source, and harvested in exponential phase (Phe1_long, DBF1_long, etc. triplicates). 3. Comparison of transcriptome of RW1 cells grown continuously in chemostat on phenylalanine as carbon-limited substrate, with cells that have experienced instant exposure to phenylalanine plus DBF. This is done by pulsing DBF to maximum solubility and a simultaneous change in feed medium to Phe+ DBF. Samples before transition (Phe ctrl1-chem, etc. quadruplates), after 30 min (DBF 30m1-chem, etc), 1 h, 2 h and 6 h (DBF6h1-chem, etc.).

2012-04-17 | E-GEOD-37328 | biostudies-arrayexpress

Model Bacteria Physiological Studies Dataset 1: Triplicate replete proteomes for Ruergeria pomeroyi DSS-3 Dataset 2: Triplicate replete proteomes for Alteromonas macleodii MIT1002

Project description:These datasets represent the global proteome of biological triplicates of replete cultures of Ruergeria pomeroyi DSS-3 and Alteromonas macleodii MIT1002 (three samples each). These datasets are an initial examination of the proteome allocation of these two heterotrophic bacteria. 2341 and 2075 proteins were identified in DSS-3 and MIT1002, respectively.

2022-06-10 | PXD034365 | Pride

Phosphoproteomic analysis of Staphylococcus aureus

Project description:S. aureus is one of the major human pathogens that greatly impacts individuals and causes a variety of illnesses ranging from minor skin infections to life-threatening diseases, such as endocarditis, pneumonia, septicemia and toxic shock syndrome. Stk1/Stp1 are particular important for S. aureus pathogenesis and survival as they are thought to participate in regulating virulence, cell wall structure and antibiotic resistance. Understanding how Ser/Thr phosphorylation regulates virulence and antibiotic resistance will provide foundation for the development of novel therapeutic strategies against S. aureus infection. The phosphoproteomic analysis of Staphylococcus aureus Newman strain led to the identification of 76 peptides with mapped phosphorylation sites belonging to 29 distinct proteins. In the case of Stk1, only one peptide (residues 157-182), with the sequence ALSETSLTQTNHVLGTVQYFSPEQAK, was predicted to have a cluster of six phosphorylation sites (Ser159, Thr161, Ser162, Thr164, Thr166 and Thr172). This segment overlaps with the sequence of kinase activation loop (residues 154-176) in Stk1. Further biochemical studies revealed cis autophosphorylation of Thr172 in the GT/S motif is necessary for self-activation and kinase activity of Stk1, whereas the trans autophosphorylation of other activation loop serines/threonins are essential for the optimal kinase activity of Stk1.

2018-10-24 | PXD006285 | Pride

Transcriptomic and proteomic responses of the oceanic diatom Pseudo-nitzschia granii to iron limitation

Project description:The oceanic diatom Pseudo-nitzschia granii was cultured in the laboratory under steady-state iron-replete and iron-limited conditions. Transcriptomic and proteomic analyses were performed to determine how this organism reorganizes major metabolic processes as a function of iron supply.

2018-08-21 | PXD009698 | Pride

Comparative proteomics of clinically relevant proteins in modern and traditional bread wheat cultivars

Project description:Bread wheat (Triticum aestivum L.) is one of the most valuable cereal crops for the human consumption. Its grain storage proteins greatly impact bread quality, though may cause food intolerances or allergies in susceptible individuals. Consequently, the investigation of a proteome polymorphism among wheat varieties is important to spot the genotypes, which would be promising donors for the breeding of hypoallergenic cereals. Herein, we discovered diversity of grain proteins in three Ukrainian wheat cultivars: ‘Sotnytsia’, ‘Panna’ (both modern selection) and ‘Ukrainka’ (old landrace). Firstly, proteins were isolated with a SDS-containing buffer that allowed extraction of various groups of storage proteins (glutenins, gliadins, globulins and albumins). Secondly, the proteome was profiled by the two-dimensional gel electrophoresis, revealing 810 clearly-separated gel spots. Software-assisted analysis of gel images, showed 66 differentially abundant proteins. Using multi-enzymatic digestion, followed by the tandem mass spectrometry, we identified 49 differentially accumulated proteins. Parallel ultrahigh-performance liquid chromatography profiling and direct mass spectrometry quantification complemented the results. With this approach we quantified 127 proteins, 12 being differentially abundant. Principal component analysis confirmed genotype as a major source of variation in both cases. Non-gluten fraction was the most diverse among investigated bread wheat cultivars. Information from public databases of clinically relevant plant proteins highlighted variable groups of wheat allergens/toxins. Data suggested that one of the modern cultivars contained less health affecting proteins in grain. Finally, we proposed set of genetic landmarks for the development of DNA marker system, which will enable fast and efficient assessment of medical safety of multiple wheat genotypes to facilitate breeding programs.

2020-05-20 | PXD012940 | Pride

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