Homo sapiens
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PXD006638
PROVIDER: PRJNA401719 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6000350.fastq.gz | Fastqsanger.gz | |||
| SRR6000360.fastq.gz | Fastqsanger.gz | |||
| SRR6000351.fastq.gz | Fastqsanger.gz | |||
| SRR6000361.fastq.gz | Fastqsanger.gz | |||
| SRR6000352.fastq.gz | Fastqsanger.gz |
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Project description:Excision of the N-terminal initiator methionine (iMet) residue from nascent peptide chains is an essential and omnipresent protein modification carried out by methionine aminopeptidases (MetAPs) that accounts for a major source of N-terminal proteoform diversity. While MetAP2 is known to be implicated in processes such as angiogenesis and proliferation in mammals, the physiological role of MetAP1 is much less clear. In this report we studied the omics-wide effects of human MetAP1 deletion and general MetAP inhibition. The levels of iMet retention are inversely correlated with cellular proliferation rates. Further, despite the increased MetAP2 expression observed upon MetAP1 deletion and as inferred from the iMet retention profiles observed, MetAP2 was unable to restore processing of MS-, MP- and MA- N-termini, indicating the higher activity of MetAP1 over these N-termini. Proteome and transcriptome expression profiling point to differential expression of proteins implicated in lipid metabolism, cytoskeleton organization, cell proliferation and protein synthesis upon perturbation of MetAP activity.
2018-01-12 | GSE103405 | GEO
Project description:Excision of the N-terminal initiator methionine (iMet) from nascent peptide chains is an essential and omnipresent protein modification carried out by Methionine aminopetidases (MetAPs) and accounting for a major source of N-terminal proteoform diversity. While MetAP2 is known to be implicated in processes such as angiogenesis and proliferation in mammals, the physiological role of MetAP1 is much less clear. In this report we studied the omics-wide effects of MetAP1 deletion and MetAP inhibition in general. While the levels of iMet retention are inversely correlated with cellular proliferation rates, deletion of MetAP1 was in part rescued by the increased MetAP2 expression and activity profiles observed.
2018-01-10 | PXD006638 | Pride
Project description:To understand the impact of alternative translation initiation on a proteome, we performed the first study on protein turnover using positional proteomics and ribosome profiling to distinguish between N-terminal proteoforms of individual genes. Overall, we monitored the stability of 1,941 human N-terminal proteoforms, including 147 N-terminal proteoform pairs that originate from alternative translation initiation, alternative splicing or incomplete processing of the initiator methionine. Ribosome profiling of lactimidomycin and cycloheximide treated human Jurkat T-lymphocytes
2015-10-23 | E-GEOD-74279 | biostudies-arrayexpress
Project description:To understand the impact of alternative translation initiation on a proteome, we performed the first study on protein turnover using positional proteomics and ribosome profiling to distinguish between N-terminal proteoforms of individual genes. Overall, we monitored the stability of 1,941 human N-terminal proteoforms, including 147 N-terminal proteoform pairs that originate from alternative translation initiation, alternative splicing or incomplete processing of the initiator methionine.
2015-10-23 | GSE74279 | GEO
Project description:We report the application of RNA-seq for profiling gene transcription upon treatment of methyl bestatin (MeBs, aminopeptidase inhibitor) or brefeldin A (BFA, ER-to-Golgi transport inhibitor), compared to DMSO control. We found MeBs and BFA similarly upregulated genes pertinent to proteotoxic stress.
2022-11-15 | GSE200454 | GEO
Project description:Most eukaryotic proteins are N-terminally acetylated, but the functional impact on a global scale has remained obscure. Using genome-wide CRISPR knockout screens in human cells, we reveal a strong genetic dependency between a major N-terminal acetyltransferase and specific ubiquitin ligases. Biochemical analyses uncover that both the ubiquitin ligase complex UBR4-KCMF1 and the acetyltransferase NatC recognize proteins bearing an unacetylated N-terminal methionine followed by a hydrophobic residue. NatC KO-induced protein degradation and phenotypes are reversed by UBR knockdown, demonstrating the central cellular role of this interplay. We reveal that loss of Drosophila NatC is associated with male sterility, reduced longevity, and age-dependent loss of motility due to developmental muscle defects. Remarkably, muscle-specific overexpression of UbcE2M, one of the proteins targeted for NatC KO mediated degradation, suppresses defects of NatC deletion. In conclusion, NatC-mediated N-terminal acetylation acts as a protective mechanism against protein degradation, which is relevant for increased longevity and motility.
2023-09-18 | GSE221447 | GEO
Project description:Here we describe our unprecedented approach in proposing parsley (PAR) as a nutraceutical intervention in inflammatory bowel disease (IBD) using a mouse model of dextran sodium sulphate (DSS)-induced colitis, following a multi-integrated-omics analysis. PAR supplementation (n=7) significantly improved colon shortening and increased the disease activity index compared to the DSS group (n=7). The colonic transcriptome revealed the down-regulation of inflammatory cytokines, and the hepatic transcriptome and metabolome revealed the up-regulation of fatty acid synthesis genes, thereby improving body weight loss. Down-regulated cancer markers were observed in the hepatic transcriptome and proteome. A global plasma metabolite analysis indicated shifts in the citric cycle and urea cycle, implicating improved impaired glycolysis and oxidative stress. Our integration of three omics analyses highlighted the involvement of the methionine-recycling pathway and PARM-bM-^@M-^Ys role in decreasing the risk of IBD. This pioneering use of multi-integrated-omics in the evaluation of nutrientsM-bM-^@M-^Y effects on physiology is expected to be widely useful and informative, shaping the future of nutritional research. Here we describe our unprecedented approach in proposing parsley (PAR) as a nutraceutical intervention in inflammatory bowel disease (IBD) using a mouse model of dextran sodium sulphate (DSS)-induced colitis, following a multi-integrated-omics analysis. PAR supplementation (n=7) significantly improved colon shortening and increased the disease activity index compared to the DSS group (n=7). The colonic transcriptome revealed the down-regulation of inflammatory cytokines, and the hepatic transcriptome and metabolome revealed the up-regulation of fatty acid synthesis genes, thereby improving body weight loss. Down-regulated cancer markers were observed in the hepatic transcriptome and proteome. A global plasma metabolite analysis indicated shifts in the citric cycle and urea cycle, implicating improved impaired glycolysis and oxidative stress. Our integration of three omics analyses highlighted the involvement of the methionine-recycling pathway and PARM-bM-^@M-^Ys role in decreasing the risk of IBD. This pioneering use of multi-integrated-omics in the evaluation of nutrientsM-bM-^@M-^Y effects on physiology is expected to be widely useful and informative, shaping the future of nutritional research. Total hepatic and colonic RNA from each respective group were pooled (n=7). The microarray analysis was carried as out as described by Jia et al. 8 Mouse Genome 430 2.0 Array GeneChips (Affymetrix, Santa Clara, CA) containing over 30,000 gene probe sets were used for genome-wide expression profiling.
2014-01-24 | E-GEOD-54349 | biostudies-arrayexpress
Project description:Besides being building blocks for protein synthesis, amino acids serve a wide variety of cellular functions, including acting as metabolic intermediates for ATP generation and for redox homeostasis. Upon amino acid deprivation, free uncharged tRNAs trigger GCN2-ATF4 to mediate the well-characterized transcriptional amino acid response (AAR). However, it is not clear whether the deprivation of different individual amino acids triggers identical or distinct AARs. Here, we characterized the global transcriptional response upon deprivation of one amino acid at a time. With the exception of glycine, which was not required for the proliferation of MCF7 cells, we found that the deprivation of most amino acids triggered a shared transcriptional response that included the activation of ATF4, p53 and TXNIP. However, there was also significant heterogeneity among different individual AARs. The most dramatic transcriptional response was triggered by methionine deprivation, which activated an extensive and unique response in different cell types. We uncovered that the specific methionine-deprived transcriptional response required creatine biosynthesis. This dependency on creatine biosynthesis was caused by the consumption of S-Adenosyl-L-methionine (SAM) during creatine biosynthesis that helps to deplete SAM under methionine deprivation and reduces histone methylations. As such, the simultaneous deprivation of methionine and sources of creatine biosynthesis (either arginine or glycine) abolished the reduction of histone methylation and the methionine-specific transcriptional response. Arginine-derived ornithine was also required for the complete induction of the methionine-deprived specific gene response. Collectively, our data identify a previously unknown set of heterogeneous amino acid responses and reveal a distinct methionine-deprived transcriptional response that results from the crosstalk of arginine, glycine and methionine metabolism via arginine/glycine-dependent creatine biosynthesis. RNA was extracted by RNAeasy kits (Qiagen) from the MCF7 or PC3 cells which exposed to the control full DMEM or deprived one (or all) amino acid media for 24 or 48 hours.
2015-04-01 | E-GEOD-62673 | biostudies-arrayexpress
Project description:Co-translational N-terminal (Nt-) acetylation of nascent polypeptides is catalyzed by N-terminal acetyltransferases (NATs). The very N-terminal amino acid sequence is the major factor determining whether or not a given protein is Nt-acetylated. In humans, six different NATs, denoted NatA-NatF, are identified. In the current study we used N-terminal COFRADIC analysis to define the in vivo substrate specificity of Naa50 (Nat5)/NatE as this has long remained elusive. Three yeast strains were generated; a control strain endogenously expressing yNaa50, a deletion strain depleted of yNaa50 and a strain deleted of yNaa50 but ectopically expressing human Naa50. When comparing the Nt-acetylation status of different N-termini in the control strain with the deletion strain, a reduction in Nt-acetylation for several yeast proteins was observed. To our surprise, these substrates were not of the predicted NatE-type substrates, but rather canonical NatA substrates. Further, ectopic expression of hNaa50 mainly resulted in the Nt-acetylation of a selected class of otherwise Nt-free yeast N-termini besides increasing the degree of Nt-acetylation of several other yeast proteins, and as such (partially) complementing those N-termini displaying reduced Nt-acetylation upon yNAA50-deletion. The preferred substrates of hNaa50 were predominantly Met-starting N-termini including Met-Lys-, Met-Val-, Met-Ala-, Met-Tyr-, Met-Phe-, Met-Leu-, Met-Ser- and Met-Thr, and highly overlapped with the previously identified human Naa60/NatF substrate specificity profile. Identification of several hNaa50 substrates with a small amino acid in the second position also revealed a potential interplay between the NATs and methionine aminopeptidases (MetAPs). The initiator Methionine (iMet) is normally cleaved off by MetAPs when the second amino acid is small, but our in vitro data suggest that in contrast to a free iMet, an Nt-acetylated iMet is not hydrolyzed by MetAPs. Thus, Naa50-mediated Nt-acetylation may potentially act as a mechanism to retain the iMet of proteins with a small amino acid at the second position that normally would be hydrolyzed.
2015-05-29 | PXD001437 | Pride
Project description:The genome-wide transcriptional response of S. cerevisiae cells upon transfer to methionine-restricted media is investigated. DHO strain (BY4742 background) was cultivated batch-wise in SDC media at 30C and 180 rpm up to mid-exponential phase (OD600 ~ 0.6). The cells of the main culture were divided in three aliquots at the mid-exponential phase, centrifuged at 6000 rpm for 5 min, washed twice with deionized and distilled sterile water prior to their transfer to the treatment media. Treatment media comprised of SDC + 0.75% methionine for the methionine-restricted case while SDC is used for the control case. Sample collection for transcriptional profiling was done at the 2nd hour of the transfer. The experiments were carried out in biological triplicates.
2024-01-01 | E-MTAB-12860 | biostudies-arrayexpress