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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.

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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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Effects of PAK4 deficiency on the transcriptome of hepatic stellate cells

Project description:Hepatic stellate cell (HSC) activation plays a pivotal role in the progression of liver fibrosis. We investigated how the loss of p21-activated kinase 4 (PAK4), an emerging therapeutic target, influences key features of HSCs. To elucidate the underlying molecular mechanisms, we carried out RNA-sequencing using PAK4-deficient HSCs.

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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.

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Effect of Pak4 ablation on transcriptome in liver of fasted mice

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Effects of PAK4 deficiency on the transcriptome of hepatic stellate cells

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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.

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