Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Cdk1 regulates cell-cell junction organization throughout the cell cycle to maintain epithelial barrier integrity

ABSTRACT: Cdk1 is a master regulator of cell cycle progression and associated changes in cell shape, functions that have primarily been studied in single cells. However, cells exist within tissues, where cell cycle-associated shape changes must occur without compromising tissue function. As such, epithelial cells are tightly connected to form protective barriers, yet how epithelial cell-cell junctions are modulated throughout the cell cycle to maintain barrier function remains unclear. Here, we show that a pool of Cdk1 localizes to cell-cell contacts in epithelial cells and phosphorylates substrates at this cellular location throughout the cell cycle. Proteomic analysis identifies these Cdk1 substrates as components of cell-cell adhesion complexes. We demonstrate that Cdk1 activity controls the organization of cell-cell junctions and consequently is essential for preserving integrity of the epithelial barrier. These findings expand the role of Cdk1 to the regulation of cell-cell adhesion, establishing a direct link between the cell cycle machinery and epithelial integrity.

INSTRUMENT(S):

ORGANISM(S): Canis Familiaris (dog) (canis Lupus Familiaris)

SUBMITTER: Harmjan Vos

LAB HEAD: Martijn Gloerich

PROVIDER: PXD063102 | Pride | 2026-06-12

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	20200714_F1_RS_LDG_0334_F1_F1.raw	Raw
	20200714_F1_RS_LDG_0334_F1_F2.raw	Raw
	20200714_F1_RS_LDG_0334_F1_F3.raw	Raw
	20200714_F1_RS_LDG_0334_F2_F1.raw	Raw
	20200714_F1_RS_LDG_0334_F2_F2.raw	Raw

Items per page:

1 - 5 of 13

Similar Datasets

Transcriptomic and proteomic profiling of KEAP1 disrupted and sulforaphane treated human breast epithelial cells

Project description:Sulforaphane (SFN), an isothiocyanate found in cruciferous vegetables, is a potent inhibitor of experimental mammary carcinogenesis and may be an effective, safe chemopreventive agent for use in humans. SFN acts in part on the Keap1/Nrf2 pathway to regulate a battery of cytoprotective genes. In this study transcriptomic and proteomic changes in the estrogen receptor negative, non tumorigenic human breast epithelial MCF10A cell line were analyzed following SFN treatment or KEAP1 knockdown with siRNA using microarray and stable isotopic labeling with amino acids in culture (SILAC), respectively. Changes in selected transcripts and proteins were confirmed by PCR and Western blot in MCF10A and MCF12A cells. There was strong correlation between the transcriptomic and proteomic responses in both the SFN treatment (R=0.679, P<0.05) and KEAP1 knockdown (R=0.853, P<0.05) experiments. Common pathways for SFN treatment and KEAP1 knockdown were xenobiotic metabolism and antioxidants, glutathione metabolism, carbohydrate metabolism and NADH/NADPH regeneration. Moreover, these pathways were most prominent in both the transcriptomic and proteomic analyses. The aldo-keto reductase family members, AKR1B10, AKR1C1, AKR1C2 and AKR1C3, as well as NQO1 and ALDH3A1, were highly upregulated at both the transcriptomic and proteomic level. Collectively, these studies served to identify potential biomarkers that can be used in clinical trials to investigate the initial pharmacodynamic action of SFN in the breast. MCF10A cells were treated with SFN or had KEAP1 knocked down by siRNA.

2011-04-22 | E-GEOD-28813 | biostudies-arrayexpress

A PTPB1-Cdk3 signaling axis promotes cell cycle progression of human glioblastoma cells through an Rb-E2F dependent pathway

Project description:Protein tyrosine phosphatase 1B (PTP1B) plays a key role in developing different types of cancer. However, the molecular mechanism underlying this effect is unclear. To identify possible molecular targets of PTP1B that mediate its positive role in tumorigenesis, we undertook a SILAC-based phosphoproteomic approach, which allowed us to identify the Cyclin-dependent kinase 3 (Cdk3) as a novel PTP1B substrate. Molecular docking studies revealed stable interactions between the PTP1B catalytic domain and Cdk3. In addition, we observed that PTP1B dephosphorylates Cdk3 at Tyrosine residue 15 in vitro and interacts with it in the nucleus and cytoplasm of human glioblastoma (GB) cells. Finally, we found that the pharmacological inhibition of PTP1B or its depletion with siRNA leads to cell cycle arrest with the diminished activity of Cdk3, the consequent hypophosphorylation of Rb, and the down-regulation of E2F and its target genes Cdk1, Cyclin A, and Cyclin E1. These data delineate a novel signaling pathway from PTP1B to Cdk3 required for efficient cell cycle progression in an Rb-E2F dependent manner in human GB cells and suggest new therapeutic strategies for treating these tumors.

2023-12-05 | PXD046000 | Pride

Effect of Cell cycle regulator CDK1 on Cell Differentiation (RNA-IP CDK1 inh KD)

Project description:Effect of Cell cycle regulator CDK1 on Cell Differentiation (RNA-IP CDK1 inh KD)

| PRJNA541529 | ENA

E-cadherin mechanotransduction activates EGFR/ERK signaling by inducing ligand shedding

Project description:The behavior of cells is governed by signals originating from their local environment, including mechanical forces that cells experience. Forces are transduced by mechanosensitive proteins, which can impinge on signaling cascades that are also activated by growth factor receptors upon ligand binding. However, the interplay between these mechanical and biochemical signals in the regulation of intracellular signaling networks remains incompletely understood. To elucidate this mechanochemical crosstalk, we conducted phosphoproteomic and transcriptomic analyses on epithelial cells subjected to mechanical strain. This approach revealed ERK signaling as a predominant hub activated in response to intercellular forces, initiated at the level of the upstream EGF receptor. Strain-induced EGFR/ERK signaling relies on mechanosensitive E-cadherin adhesions, as it is disrupted upon genetic modulation of force transduction by the E-cadherin complex. Proximity labeling identified a connection between E-cadherin and ADAM17, an enzyme that mediates the shedding of soluble EGFR ligands. We developed a novel ADAM probe that showed that mechanical strain induces ADAM17 activity, which is essential for relaying forces to EGFR/ERK signaling. Collectively, our data demonstrate how forces transduced by E-cadherin adhesion modulate the presence of EGFR ligands to regulate downstream ERK activity. Our findings illustrate how intercellular forces and biochemical ligands can operate within a single, linear signaling cascade.

2025-11-18 | PXD052926 | Pride

Phosphoproteome analysis reveals the importance of Greatwall-endosulfine pathway to regulate cell-cycle progression upon the rapamycin-induced autophagy

Project description:Protein phosphorylation plays an important role in the process of autophagy. Autophagy is associated with cell cycle, which is controlled by the balance between the cyclin-dependent kinases and phosphatases activities. However, up to now, the signal transduction pathways that underlied rapamycin-induced autophagy and cell cycle have remained elusive. Here, we used stable isotope labeling of amino acids in cell culture and high-throughput quantitative mass spectrometry to perform a global proteome and phosphoproteome analysis of rapamycin-induced autophagy in vitro. By monitoring proteome and phosphoproteome alterations with rapamycin treatment, we detected downregulation of mTOR signaling pathway and confirmed the occurrence of autophagy. Additionally, spliceosome and nuclear pore complexes were enriched to be regulated, which further validated autophagy as a stress response itself. More importantly, we discovered that mTORC1 could control cell cycle progression though Greatwall-endosulfine-PP2A pathway in HeLa cells. Firstly, we found the elevated profile of cell cycle-related substrates and determined the enrichment of CDK1, MAPK1 and MAPK3 kinases, which implied the activation of these kinases. Secondly, Pathway interrogation using kinase inhibitor treatment confirmed the effect of mTOR inhibition on CDK1 activity and cell cycle progression. Thirdly, we discovered that Greatwall-endosulfine complex was required to mediate mTOR-mediated cell-cycle progression. In conclusion, we presented a high-confidence map of phosphoproteomic of autophagy and unveiled the Greatwall-endosulfine pathway to regulate cell-cycle progression in the rapamycin-induced autophagy.

2021-04-06 | PXD014737 | Pride

Rapid Aldosterone Effects in Mouse Kidney Distal Convoluted Tubules Cells

Project description:Kidney distal convoluted tubules (DCT) are important for regulation of urinary salt excretion. Aldosterone is known to exert long-term effects in this segment, and regulate sodium reabsorption via increasing abundance of the Na+-Cl- cotransporter (NCC) and the epithelial Na channel ENaC. Whether acute effects of aldosterone occur in the DCT and the potential signaling networks remain unknown. Here in this study, we aim to identify the acute aldosterone-mediated signaling (rapid effects) in the DCT.

2019-06-24 | PXD010032 | Pride

RNA-seq of cardiac-specific Cdk1 knockout mice at 3 weeks after experimental myocardial infarction

Project description:Biological Relevance and Intent of the Experiment: The objective of this study is to elucidate the role of Cdk1 in cardiac function, specifically its contribution to cardiomyocyte proliferation and response to injury. Using a heart-specific Cdk1 knockout mouse model, we investigate the molecular and cellular impact of Cdk1 deficiency in the context of myocardial infarction (MI). Cdk1 is known for its regulatory functions in cell cycle progression, and its absence may significantly affect cardiac repair mechanisms post-MI. This research aims to explore whether the lack of Cdk1 impairs cardiomyocyte regeneration or promotes maladaptive remodeling, leading to compromised cardiac function.

2024-12-02 | E-MTAB-14508 | biostudies-arrayexpress

Cdk1 controls global epigenetic landscape in embryonic stem cells

Project description:The cyclin-dependent kinase 1 (Cdk1) represents an ancient cell cycle kinase that has been conserved from yeast to humans. Cdk1 is the only essential mammalian Cdk, which drives cytokinesis by phosphorylating a large number of cellular proteins. To uncover additional functions of Cdk1, we generated a knock-in strain of mice expressing an analog-sensitive version of Cdk1 in place of wild-type Cdk1. These mice and cells derived from them allow us to investigate Cdk1 function in essentially any compartment and at any stage of development. In our study, we focused on embryonic stem (ES) cells, as this cell type expresses particularly high levels of Cdk1. Very unexpectedly, we found that in ES cells the majority of Cdk1 substrates are localized on chromatin. Cdk1 phosphorylates a large number of proteins involved in epigenetic regulation, including writers and erasers of all major histone marks. Consistent with this finding, inhibition of Cdk1 altered histone modification status of ES cells. High levels of Cdk1 in ES cells (and in induced pluripotent stem cells) phosphorylate and partially inactivate Dot1l, the histone H3 lysine 79 methyltransferase responsible for placing activating H3K79 marks on gene bodies. Decrease of Cdk1 activity during ES cell differentiation de-represses Dot1l, thereby allowing coordinated expression of differentiation genes. These analyses indicate that Cdk1 functions to maintain the epigenetic identity of ES cells.

2020-10-05 | PXD015173 | Pride

CDK regulated chicken chromatin

Project description:Initiation and completion of DNA replication has a major impact on chromatin, but how core chromatin processes are cell cycle regulated in somatic cells remains poorly understood. To address this question we conducted a quantitative proteomics study that took advantage of an analogue sensitive mutation in Cdk1 (cdk1as), which allows for rapid and highly specific inactivation of Cdk1 by the bulky ATP analogue 1NMPP1. Neither Cdk1 nor Cdk2 are required for S-phase progression, while inactivation of Cdk1 in Cdk2 knock-out cells causes a complete block of DNA replication initiation and S-phase progression. Here we compared chromatin fractions obtained from cdk1as and cdk1as/cdk2-/- cells two hours after Cdk1 inactivation. Statistical analysis of these four independent experiments (including 2 label swaps) identified 135 proteins that showed a significant change in SILAC ratio among a total of 2402 proteins quantified in at least three experiments. This approach led us to discover a novel functional interplay between interphase Cdks and the chromatin association of a variety of novel candidate proteins such as Cdk1 itself, the APC/C regulatory subunit cdc20, the PP4 regulatory subunit Smek2, the helicase FUBP1 and the PHD domain-containing zinc finger protein PHF6.

2014-01-29 | PXD000492 | Pride

Cdk1 Gates Cell Cycle-Dependent tRNA Synthesis by Regulating RNA Polymerase III Activity

Project description:tRNA genes are transcribed by RNA polymerase III (RNAPIII). During recent years it has become clear that RNAPIII activity is strictly regulated by the cell in response to environmental cues and the homeostatic status of the cell. However, the molecular mechanisms that control RNAPIII activity to regulate the amplitude of tDNA transcription in normally cycling cells are not well understood. Here, we show that tRNA levels fluctuate during the cell cycle and reveal the underlying molecular mechanism. The cyclin Clb5 recruits the cyclin dependent kinase Cdk1 to tRNA genes to boost tDNA transcription during S phase. At tDNA genes, Cdk1 promotes the recruitment of TFIIIC, stimulates the interaction between TFIIIB and TFIIIC, and increases the dynamics of RNA polymerase III in vivo. Furthermore, we identified Bdp1 as an important Cdk1 substrate in this process. Preventing Bdp1 phosphorylation prevented cell cycle-dependent recruitment of TFIIIC and abolished the cell cycle-induced increase in tDNA transcription. Our findings demonstrate that under optimal growth conditions Cdk1 gates tRNA synthesis in S phase by regulating the RNAPIII machinery, revealing a direct link between the cell cycle and RNAPIII activity.

2018-10-19 | PXD011084 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data