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Effect of Pak4 deficiency on transcriptomic profile in eWAT of mice

ABSTRACT: Effect of Pak4 deficiency on transcriptomic profile in eWAT of mice

PROVIDER: PRJNA887050 | ENA |

REPOSITORIES: ENA

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Effect of Pak4 deficiency on transcriptomic profile in eWAT of mice

Project description:The excessive energy is primarily stored as triacylglycerol in lipid droplets in adipocytes, which is hydrolyzed by the actions of lipases upon energy demand. In this study, the potential role of PAK4 in the lipolysis process in adipocytes was investigated. To elucidate functional outcomes, we performed RNA-sequencing analysis using littermate WT and adipose tissue-specific Pak4 KO mice in fasted conditions.

2023-10-15 | GSE214769 | GEO

Effect of Pak4 deficiency on transcriptome in liver of mice

Project description:PAK4 has emerged as a promising target for anti-cancer drug development. However, its role in oxidative stress conditions remains elusive. We investigated the effects of PAK4 signaling on hepatic ischemia/reperfusion (I/R) injury. To elucidate molecular mechanisms, we performed RNA-sequencing analysis using littermate WT and hepatocyte-specific Pak4 KO mice in I/R condition. Transcriptomic analysis enabled us to find the main signaling nodes altered by Pak4 deficiency in close association with antioxidant response.

2022-04-20 | GSE200913 | GEO

Effect of Pak4 deficiency on transcriptome in liver of mice

Project description:Effect of Pak4 deficiency on transcriptome in liver of mice

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Characterization of the PAK4 interactome by quantitative mass spectrometry

Project description:p21-activated kinase 4 (PAK4) is a serine/threonine kinase critical during development and with a proposed role in cancer and related cellular processes, including cell proliferation, survival and migration. However, while a limited number of PAK4-interacting proteins have been identified, the PAK4 interactome has not been systematically characterized. Here, we employed iTRAQ-based quantitative mass spectrometry of PAK4-immunioprecipitations from three distinct isolated cellular fractions to comprehensively profile the PAK4 interactome in human. These data will provide a valuable resource for further investigations on the role of PAK4 in physiology and disease.

2018-10-27 | PXD004086 | Pride

Effect of Pak4 ablation on transcriptome in liver of fasted mice

Project description:Hepatic ketogenesis is crucial for energy homeostasis in a fast state, whereas defective ketogenesis is associated with various diseases. We explored the role of PAK4, an oncoprotein, in ketogenesis. To investigate the molecular basis, we carried out RNA-sequencing analysis using littermate WT and hepatocyte-specific Pak4 KO mice in fasted conditions.

2023-07-31 | GSE214442 | GEO

PAK4 suppresses RELB to prevent senescence-like growth arrest in breast cancer

Project description:Overcoming cellular growth restriction, including the evasion of cellular senescence, is a hallmark of cancer. We report that PAK4 is overexpressed in all human breast cancer subtypes and associated with poor patient outcome. In mice, MMTV-PAK4 overexpression promotes spontaneous mammary cancer, while PAK4 gene depletion delays MMTV-PyMT driven tumors. Importantly, PAK4 prevents senescence-like growth arrest in breast cancer cells in vitro, in vivo and ex vivo, but is not needed in non-immortalized cells, while PAK4 overexpression in untransformed human mammary epithelial cells abrogates H-Ras-V12-induced senescence. Mechanistically, a PAK4 – RELB - C/EBPa axis controls the senescence-like growth arrest and a PAK4 phosphorylation residue (RELB-Se151) is critical for RELB-DNA interaction, transcriptional activity and expression of the senescence regulator C/EBPa. These findings establish PAK4 as a promoter of breast cancer that can overcome oncogene-induced senescence and reveal a selective vulnerability of cancer to PAK4 inhibition.

2019-07-09 | GSE112817 | GEO

Plasma DNA profile in DNASE1L3 deficiency

Project description:Plasma DNA profile in DNASE1L3 deficiency

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Genome-wide transcriptome analysis of PAK4 inhibition/knockdown in human bladder cancer cell line VMCUB1

Project description:Using multi-omic analyses, we identified PAK4 (P21 (RAC1) Activated Kinase 4) amplification and overexpression of Kinase PAK4 in a subset of bladder cancers. We confirmed the role of PAK4 in bladder cancer cell proliferation and invasion by in vitro experiments. Furthermore, our studies showed that PAK4 inhibitor is effective in curtailing bladder cancer cell growth. In order to understand the effect of PAK4 inhibition and knockdown on bladder cancer transcriptome, we performed RNA-sequencing of PAK4 siRNA transfected and PAK4 inhibitor (PF-3758309) treated bladder cancer cells (VM-CUB1). Analyses led to identification of direct targets of PAK4 in bladder cancer and associated pathways.

2020-04-20 | GSE130455 | GEO

Effects of PAK4 knockdown on gene expression in glioblastoma-associated endothelial cells

Project description:PAK4 was knocked down in human glioblastoma (GBM)-associated endothelial cells (ECs) using CRISPR-Cas9/gRNA. RNA was isolated and analyzed by RNAseq. The effects of PAK4 knockout on gene expression were determined.

2020-09-13 | GSE154133 | GEO

Functional role and therapeutic targeting of p21-associated kinase 4 (PAK4) in Multiple Myeloma

Project description:Dysregulated oncogenic serine/threonine kinases play a pathological role in diverse forms of malignancies, including multiple myeloma (MM), and thus represent potential therapeutic targets. Here, we evaluated the biological and functional role of p21-activated kinase 4 (PAK4), and its potential as a new target in MM for clinical applications. PAK4 promoted MM cell growth and survival via activation of MM survival signaling pathways, including the MEK-ERK pathway. Furthermore, treatment with orally bioavailable PAK4 allosteric modulator (KPT-9274) significantly impacted MM cell growth and survival in a large panel of MM cell lines and primary MM cells alone and in the presence of bone marrow microenvironment. Intriguingly, we have identified FGFR3 as a novel binding partner of PAK4 and observed significant activity of KPT-9274 against t(4;14)-positive MM cells. These data support PAK4 as an oncogene in myeloma, and provide the rationale for the clinical evaluation of PAK4 modulator in myeloma.

2017-01-19 | GSE93745 | GEO

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