Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

CDK9 binds and activates SGK3 to promote cardiac repair after injury via the GSK-3β/β-catenin pathway

ABSTRACT: SGK3 (threonine-protein kinase 3) is a functional kinase we identified previously with the capacity to promote cardiomyocyte proliferation and cardiac repair after myocardial infarction. However, the upstream signals regulating SGK3 are still unknown. Based on the quantitative proteomics data and pulldown assay, we identified cyclin-dependent kinase 9 (CDK9) as a novel therapeutic target in regeneration therapy.

ORGANISM(S): Mus Musculus

SUBMITTER: Liansheng Wang

PROVIDER: PXD035187 | iProX | Sat Jul 09 00:00:00 BST 2022

REPOSITORIES: iProX

ACCESS DATA

Json Xml

Publications

CDK9 binds and activates SGK3 to promote cardiac repair after injury via the GSK-3β/β-catenin pathway.

Sun Jiateng J Yang Tongtong T Wei Tianwen T Zhou Liuhua L Shan Tiankai T Chen Jiawen J Gu Lingfeng L Chen Bingrui B Liu Liu L Jiang Qiqi Q Du Chong C Ma Yao Y Wang Hao H Chen Feng F Guo Xuejiang X Ji Yong Y Wang Liansheng L

Frontiers in cardiovascular medicine 20220823

The mammalian heart possesses entire regeneration capacity after birth, which is lost in adulthood. The role of the kinase network in myocardial regeneration remains largely elusive. SGK3 (threonine-protein kinase 3) is a functional kinase we identified previously with the capacity to promote cardiomyocyte proliferation and cardiac repair after myocardial infarction. However, the upstream signals regulating SGK3 are still unknown. Based on the quantitative phosphoproteomics data and pulldown ass ...[more]

PMID: 36082129

Similar Datasets

Wnt1/?catenin injury response activates the epicardium and cardiac fibroblasts to promote cardiac repair.

Project description:Wnts are required for cardiogenesis but the role of specific Wnts in cardiac repair remains unknown. In this report, we show that a dynamic Wnt1/?catenin injury response activates the epicardium and cardiac fibroblasts to promote cardiac repair. Acute ischaemic cardiac injury upregulates Wnt1 that is initially expressed in the epicardium and subsequently by cardiac fibroblasts in the region of injury. Following cardiac injury, the epicardium is activated organ-wide in a Wnt-dependent manner, expands, undergoes epithelial-mesenchymal transition (EMT) to generate cardiac fibroblasts, which localize in the subepicardial space. The injured regions in the heart are Wnt responsive as well and Wnt1 induces cardiac fibroblasts to proliferate and express pro-fibrotic genes. Disruption of downstream Wnt signalling in epicardial cells decreases epicardial expansion, EMT and leads to impaired cardiac function and ventricular dilatation after cardiac injury. Furthermore, disruption of Wnt/?catenin signalling in cardiac fibroblasts impairs wound healing and decreases cardiac performance as well. These findings reveal that a pro-fibrotic Wnt1/?catenin injury response is critically required for preserving cardiac function after acute ischaemic cardiac injury.

| S-EPMC3261567 | biostudies-literature

Serine threonine kinase 24 (STK24) mediates immune evasion signals in tumors by regulating immuno-suppressive molecules

Project description:Serine threonine kinase 24 (STK24) mediates immune evasion signals in tumors by regulating immuno-suppressive molecules

| PRJNA820876 | ENA

Structural basis of T-loop-independent recognition and activation of CDKs by the CDK-activating kinase

Project description:Cyclin-dependent kinases (CDKs) are prototypical regulators of the cell cycle. The CDK-activating kinase (CAK) acts as a master regulator of CDK activity by catalysing the activating phosphorylation of CDKs on a conserved threonine residue within the regulatory T-loop. However, structural data illuminating the mechanism by which the CAK recognises and activates CDKs have remained elusive. Here, we determine high-resolution structures of the CAK in complex with CDK2 and CDK2-cyclin A by cryogenic electron microscopy. Our structures reveal a T-loop-independent kinase-kinase interface with contributions from both kinase lobes. Computational analysis and structures of CAK in complex with CDK1-cyclin B and CDK11 indicate that these structures represent the general architecture of CAK-CDK complexes. These results advance our mechanistic understanding of cell cycle regulation and kinase signalling cascades.

2025-10-16 | PXD068021 | Pride

DOT1L-mediated CDK9 methylation is essential for DNA double-strand break repair

Project description:P-TEFb is a key regulator of transcription elongation and is composed of cyclin-dependent kinase 9 (CDK9) and cyclin T1. DOT1L is a histone H3K79 methyltransferase. Here, we show that treatment with the DOT1L inhibitor EPZ-5676 induces transcriptome changes in HCT116 cells. We further demonstrate that DOT1L methylates CDK9 at lysine 56 and that CDK9 methylation-deficient mutant K56A reshapes genome-wide CDK9 occupancy. Notably, changes in CDK9 occupancy are particularly pronounced at double-strand break (DSB)-related genes and are associated with the regulation of their transcription. This idataset includes RNA-seq and ChIP-seq data generated from HCT116 cells.

2025-12-29 | GSE314839 | GEO

Oligomerisation-driven MLKL ubiquitylation antagonises necroptosis

Project description:Mixed lineage kinase domain-like (MLKL) is the executioner in the caspase 8-independent form of programmed cell death called necroptosis. Once Receptor Interacting serine/threonine Protein Kinase 3 (RIPK3) is activated by upstream cell death signals, it phosphorylates MLKL and triggers the oligomerization and membrane translocation required for MLKL induced membrane disruption. Besides phosphorylation, MLKL also undergoes ubiquitylation during the early stages of necroptosis, yet neither the mechanism nor the significance of this event has been demonstrated. Here we show that necroptosis-specific, multi-mono-ubiquitylation of MLKL occurs on biological membranes, and requires its activation and oligomerisation. Inactive MLKL mutants recruited to membranes during necroptosis are ubiquitylated but this results in their proteasome and lysosome dependent turnover. We identified several ubiquitylated lysines however mutation of these did not affect MLKL ubiquitylation in response to a necroptotic stimulus.

2021-04-28 | PXD015537 | Pride

Oncogenic Serine-Threonine Kinase Receptor Associated Protein Supports Hepatocellular Carcinoma Cell Growth by Enhancing Wnt/β-catenin Signaling

Project description:Serine-threonine kinase receptor-associated protein (STRAP) is upregulated in breast, colorectal and lung cancers, promoting their growth. We identify the upregulation of STRAP in hepatocellular carcinomas. Elevated STRAP endows tumor cells with growth advantage by reprograming a variety of metabolic processes and signaling pathways critical for hepatocellular carcinoma progression. Especially, enhanced Wnt/β-catenin signaling is likely to be a major effector of its tumor-promoting role.

2018-09-03 | GSE101061 | GEO

Effects of T350 phospho- on gene repression activity of EZH2

Project description:The Polycomb group (PcG) protein enhancer of zeste homolog 2 (EZH2) plays an essential role in histone methylation-mediated epigenetic gene silencing. We demonstrate that under physiological conditions, cyclin-dependent kinase 1 (CDK1) and 2 (CDK2) bind to and phosphorylate EZH2 at threonine 350 (T350) in an evolutionally conserved motif. T350 phosphorylation is required for EZH2 function in silencing of genes that promote differentiation and inhibit proliferation and migration. Blockage of T350 phosphorylation by generating a T350A mutation largely diminishes the global effect of EZH2 on gene silencing.

2010-11-02 | GSE20433 | GEO

Effect of T350 phosphorylation on gene repression activity of EZH2 in BJ cells

2010-11-10 | GSE22427 | GEO

RNA sequencing of adult cardiomyocyte cyclin C deletion

Project description:RNA sequencing of adult cardiomyocyte cyclin C deletion

| PRJNA605429 | ENA

DOT1L-mediated CDK9 methylation is essential for DNA double-strand break repair [RNA-seq]

2025-12-30 | GSE315014 | GEO