Integrated Proteogenomic Characterization of Adenocarcinoma of the esophagogastric junction
Ontology highlight
ABSTRACT:
INSTRUMENT(S): autoflex
ORGANISM(S): Homo Sapiens (human)
SUBMITTER: 
Li Yuan
LAB HEAD: Xiang-Dong Cheng
PROVIDER: PXD030667 | Pride | 2022-11-14
REPOSITORIES: Pride
Similar Datasets
Project description:Systemic lupus erythematosus (SLE) is a systemic and heterogeneous autoimmune disease for which its treatment and phosphorylation-dependent regulatory mechanism remain elusive. Here, we aim to explore the molecular mechanism of phosphorylation regulation for SLE. We employed high-throughput Phosphoproteomics of peripheral blood mononuclear cells (PBMCs) from 126 patients with SLE remission stage (SLE_S), 70 patients with SLE active stage (SLE_A), 160 patients with RA, and 135 healthy controls (HC). An independent cohort that included 60 SLE_S, 35 SLE_A, 50 RA and 40 HC was used to validate the phosphosites via parallel reaction monitoring (PRM). We revealed upregulated pathways involved in cell adhesion and migration in patients with SLE (SLE_S and SLE_A) compared with HCs and RA. Expression pattern clustering analysis revealed several specifically upregulated phosphosites, and the leukocyte transendothelial migration was specifically enriched in SLE_A. We predicted several key kinases including MAP3Ks, MAP2Ks, IKKB and TBK1, and found that upregulated kinase activity is associated with increased phosphorylation of VCL, TLN1 and VAPB by kinases-substrate network analysis. These phosphorylated proteins also regulate the pathways related to cell adhesion and migration, and which have not been implicated in previous studies of SLE. Moreover, we validated these phosphosites with the same trend as 4D-LFQ data, including LCP1 S5, TLN1 S1201, TLN1 S1225, VCL S275 and VCL S579. In summary, the present study elucidates the changes of phosphosites, kinases and pathways in SLE, and may provide potentially novel targets for further mechanism exploration.
2023-03-11 | PXD025076 | Pride
Project description:Systemic lupus erythematosus (SLE) is a systemic and heterogeneous autoimmune disease for which its treatment and phosphorylation-dependent regulatory mechanism remain elusive. Here, we aim to explore the molecular mechanism of phosphorylation regulation for SLE. We employed high-throughput Phosphoproteomics of peripheral blood mononuclear cells (PBMCs) from 126 patients with SLE remission stage (SLE_S), 70 patients with SLE active stage (SLE_A), 160 patients with RA, and 135 healthy controls (HC). An independent cohort that included 60 SLE_S, 35 SLE_A, 50 RA and 40 HC was used to validate the phosphosites via parallel reaction monitoring (PRM). We revealed upregulated pathways involved in cell adhesion and migration in patients with SLE (SLE_S and SLE_A) compared with HCs and RA. Expression pattern clustering analysis revealed several specifically upregulated phosphosites, and the leukocyte transendothelial migration was specifically enriched in SLE_A. We predicted several key kinases including MAP3Ks, MAP2Ks, IKKB and TBK1, and found that upregulated kinase activity is associated with increased phosphorylation of VCL, TLN1 and VAPB by kinases-substrate network analysis. These phosphorylated proteins also regulate the pathways related to cell adhesion and migration, and which have not been implicated in previous studies of SLE. Moreover, we validated these phosphosites with the same trend as 4D-LFQ data, including LCP1 S5, TLN1 S1201, TLN1 S1225, VCL S275 and VCL S579. In summary, the present study elucidates the changes of phosphosites, kinases and pathways in SLE, and may provide potentially novel targets for further mechanism exploration.
2023-03-11 | PXD025399 | Pride
Project description:Systemic lupus erythematosus (SLE) is a systemic and heterogeneous autoimmune disease for which its treatment and phosphorylation-dependent regulatory mechanism remain elusive. Here, we aim to explore the molecular mechanism of phosphorylation regulation for SLE. We employed high-throughput Phosphoproteomics of peripheral blood mononuclear cells (PBMCs) from 126 patients with SLE remission stage (SLE_S), 70 patients with SLE active stage (SLE_A), 160 patients with RA, and 135 healthy controls (HC). An independent cohort that included 60 SLE_S, 35 SLE_A, 50 RA and 40 HC was used to validate the phosphosites via parallel reaction monitoring (PRM). We revealed upregulated pathways involved in cell adhesion and migration in patients with SLE (SLE_S and SLE_A) compared with HCs and RA. Expression pattern clustering analysis revealed several specifically upregulated phosphosites, and the leukocyte transendothelial migration was specifically enriched in SLE_A. We predicted several key kinases including MAP3Ks, MAP2Ks, IKKB and TBK1, and found that upregulated kinase activity is associated with increased phosphorylation of VCL, TLN1 and VAPB by kinases-substrate network analysis. These phosphorylated proteins also regulate the pathways related to cell adhesion and migration, and which have not been implicated in previous studies of SLE. Moreover, we validated these phosphosites with the same trend as 4D-LFQ data, including LCP1 S5, TLN1 S1201, TLN1 S1225, VCL S275 and VCL S579. In summary, the present study elucidates the changes of phosphosites, kinases and pathways in SLE, and may provide potentially novel targets for further mechanism exploration.
2023-03-11 | PXD025559 | Pride
Project description:WDR6 was a scaffolding/ regulatory protein that interacts with diverse signaling molecules. Our findings showed that WDR6 might be involved in post-translational modifications (PTMs). Then we performed transcriptomic analysis of primary hepatocytes from WDR6-WKO and control mice.
2023-09-22 | PXD034542 | Pride
Project description:Protein phosphatase 6 (PP6) is a member of the PP2A-like subfamily, which plays significant roles in numerous fundamental biological activities. We found that PPP6C plays important roles in male germ cells recently. Spermatogenesis is supported by the Sertoli cells in seminiferous epithelium. In this study, we crossed Ppp6cF/F mice with AMH-Cre mice to gain mutant mice with specific depletion of the Ppp6c gene in the Sertoli cells. We discovered that the PPP6C cKO male mice were absolutely infertile and germ cells were largely lost during spermatogenesis. By combing phosphoproteome with bioinformatics analysis, we showed that the phosphorylation status of β-catenin at S552 (a marker of adherens junctions) was significantly upregulated in mutant mice. Abnormal β-catenin accumulation resulted in impaired testicular junction integrity, thus led to abnormal structure and functions of BTB. Taken together, our study reveals a novel function for PPP6C in male germ cell survival and differentiation by regulating the cell-cell communication through dephosphorylating β-catenin at S552.
2022-02-15 | PXD028051 | Pride
Project description:Phosphorylation is well-known in regulating various biological processes. However, comprehensively phosphoproteomic profiling in the termination of liver regeneration (LR) is still missing. Here, we used TMT labeling coupled with phosphopeptides enrichment and 2D LC-MS/MS analysis to establish a global phosphoproteomic map in mice liver at day 5 after partial hepatectomy. Altogether, 619 phosphorylation sites in 437 proteins were significantly up-regulated and 503 phosphorylation sites in 358 proteins were down-regulated. The differentially phosphorylated proteins were further classified according to their biological process, cellular components, molecular function and subcellular localization. KEGG pathway analysis showed that they mainly participate in metabolic pathways, DNA replication, tight junction and focal adhesion. Motif analysis of the identified phosphorylation sites has revealed a diverse array of consensus sequences, suggesting multiple kinase families such as MAPK, PKA/PKC, CaMK-II, CKII and CDK, may be involved in the termination of LR. Finally, several differentially phosphorylated proteins were validated by Co-immunoprecipitation and Western blot. Taken together, our data unravels the first comprehensive phosphoproteomic map in the termination of liver regeneration in mice, which greatly expands our knowledge in the complicate regulation of this process and provides new directions on the treatment of liver cancer using liver resection and donor liver transplantation. Biological significance: The novelty of this study is that we have established for the first time a global phosphoproteomic map in mice liver at day 5 after partial hepatectomy, which represents the termination of liver regeneration. Altogether, 9,775 phosphorylation sites in 3,458 proteins were identified, among which 7,738 phosphorylation site in 2,971 proteins were quantified. KEGG pathway analysis demonstrates markedly metabolic reprograming in termination of LR, which is further validated by selected validation of several differentially phosphorylated metabolic enzymes such as PDHA, ACACA and FASN. The consistent high phosphorylation of PDHA in the first 4 days and its rapidly decreased phosphorylation at day 5 after PH might be a key signal in controlling the switch between glycolysis and oxidative
2020-03-04 | PXD011374 | Pride
Project description:Protein phosphatases are post-translational regulators of Toxoplasma gondii proliferation, tachyzoite-bradyzoite differentiation and pathogenesis. Here, we identify the putative protein phosphatase 6 (TgPP6) subunits of T. gondii and elucidate their role in the parasite lytic cycle. The putative catalytic subunit TgPP6C and regulatory subunit TgPP6R likely form a complex whereas the predicted structural subunit TgPP6S, with low homology to the human PP6 structural subunit, does not coassemble with TgPP6C and TgPP6R. Functional studies showed that TgPP6C and TgPP6R are essential for parasite growth and replication. The ablation of TgPP6C significantly reduced the synchronous division of the parasite's daughter cells during endodyogeny, resulting in disordered rosettes. Moreover, the six conserved motifs of TgPP6C were required for efficient endodyogeny. Phosphoproteomic analysis revealed that ablation of TgPP6C predominately altered the phosphorylation status of proteins involved in the regulation of the parasite cell cycle. Deletion of TgPP6C significantly attenuated the parasite virulence in mice. Immunization of mice with TgPP6C-deficient type I RH strain induced protective immunity against challenge with a lethal dose of RH or PYS tachyzoites and Pru cysts. Taken together, the results show that TgPP6C contributes to the cell division, replication and pathogenicity in T. gondii.
2023-11-28 | PXD041907 | Pride
Project description:Through the quantitative proteomics research strategy of TMT labeling and phosphorylation enrichment technology and high-resolution liquid chromatography-mass spectrometry, this project carried out the quantitative research of phosphorylated proteomics. In this study, a total of 6227 phosphorylation sites were identified, of which 4501 sites contained quantitative information. In order to ensure the high reliability of the results, we used the standard of localization probability>0.75 to filter the identification data, and finally determined 4842 phosphorylation sites located on 2328 proteins, of which 4,011 sites of 1996 proteins contained quantitative Information, and use the filtered data for subsequent bioinformatics analysis. If 1.5 times is the change threshold, t-test p-value<0.05 is the standard, and after full proteomics normalization, then among the quantified phosphorylation sites, there are 161 in the AC-B4vsAC-MG comparison group The modification level of the locus was up-regulated, and the modification level of 364 sites was down-regulated (for more information about the differences between the comparison groups, please see the main body of the report). Based on the above data, we conducted a systematic bioinformatics analysis of proteins containing quantitative information, including protein annotation, functional classification, functional enrichment, and cluster analysis based on functional enrichment. And combining the above information provides a reference direction for the downstream in-depth research based on proteomics.
2022-02-17 | PXD027844 | Pride
Project description:Clostridium acetobutylicum has been extensively exploited to produce biofuels and solvents and its biofilm could dramatically improve its productivities. However, genetic control of C. acetobutylicum biofilm has not been dissected so far. Here, a total of 24 disruptants were finally obtained over several years of attempts. Biofilm formation and physiological phenotypes were characterized for these disruptants and most of them showed robust biofilm formation still, or showed both impaired biofilm formation and cell growth. Only a mutant with a disputed histidine kinase gene (CA_C2730, designated bfcK in this study) abolished biofilm formation without impaired cell growth or solvent production. Phosphoproteomic analysis revealed that bfcK could control C. acetobutylicum flagellar motility at both translational and post-translational (protein phosphorylation) levels. The bfcK also showed apparent regulation of a serine/threonine protein kinase (encoded by CA_C0404) which was involved in protein secretion. Based on these findings, possible bfcK-based mechanisms for biofilm formation in C. acetobutylicum were proposed.
2021-07-30 | PXD021161 | Pride
Project description:Insufficient leaf photosynthesis promotes sheath NSC transport to the panicle during grain filling. SnRK1 regulates assimilate distribution between plant tissues and organs. However, the mechanism by which SnRK1 regulates sheath NSC transport to the panicle and its response to limited leaf assimilation remain unclear. Here, we performed leaf cutting (LC) at anthesis to simulate insufficient leaf assimilation and set no treatment as a CK. In response to LC, SnRK1 activity increased rapidly, and NSC transport was advanced. Sheath NSCs were not transported in a snrk1a mutant with deficient SnRK1 activity. These results indicated that SnRK1 activity is important for sheath NSC transport. The high correlation of T6P and sucrose and the inhibition of SnRK1 by T6P in sheaths in vitro implied that T6P slightly inhibits SnRK1 activity in rice sheaths in response to sucrose availability. The increase in SnRK1 activity was accompanied by an increase in OsSnRK1a expression and a low sucrose content. Low sucrose signaling increases SnRK1 transcription. Therefore, we speculated that OsSnRK1a expression positively regulates SnRK1 activity in response to low sucrose availability in rice sheaths. Through phosphoproteomics and further PRM verification, 20 phosphosites that depend on SnRK1 and are correlated with NSC transport were obtained. Based on the function of these sites and proteins, we found that SnRK1 regulates starch degradation, sucrose metabolism, phloem transport, sugar transport across tonoplast, and glycolysis via phosphorylation to promote sheath NSC transport. Overall, our results revealed the importance, function and regulatory mechanism of SnRK1 in sheath NSC transport.
2022-03-18 | PXD024670 | Pride