Project description:RNA-seq was performed on liver tissues from PTENα knockout and wild-type mice following LPS stimulation. The study aims to characterize gene expression changes associated with hepatic inflammatory responses in the absence of PTENα.
Project description:To determine the changes in peritoneal immune cells upon PTENα deficiency, we performed scRNA-seq to analyze the peritoneal immune microenvironment in wild-type (WT) and PTENα knockout (KO) mice.
Project description:To explore the binding sites of PTENα on viral or host RNAs, we performed HyperTRIBE assay of HEK293T cells overexpressing ADAR1-CD, PTENα-N(WT)-ADAR1-CD, or PTENα-N(6R/D)-ADAR1-CD fusion protein under VSV-GFP (green fluorescent protein-expressing vesicular stomatitis virus) infection.
Project description:In contrast to the ubiquitous expression profile of PTEN, PTENα is predominantly expressed in brain. To study the biological function of PTENα in brain, we employed LCMV to induce murine viral encephalitis model. Through single cell RNA sequencing, we revealed the immunological function of PTENα during viral infection in the brain.
Project description:As a tumor suppressor, PTEN is frequently mutated in human cancers and PTEN mutants promote tumor progression and metastasis. PTEN mutations have been implicated in immune regulation, but the underlying mechanism is largely unknown. We report that PTENα, the isoform of PTEN, remains active in cancer bearing stop-gained PTEN mutations. Through counteraction of CD8+ T cell-mediated cytotoxicity, presence of PTENα leads to T cell dysfunction and accelerates immune-resistant cancer progression. Clinical analysis further uncovers that PTENα-active mutations suppress host immune responses and result in poor prognosis in cancer as relative to PTENα-inactive mutations. Furthermore, germline deletion of Ptenα in mice increases cell susceptibility to immune attack through augmenting stress granule formation and limiting synthesis of peroxidases, leading to massive oxidative cell death and severe inflammatory damage. We propose that PTENα protects tumor from T cell killing and thus PTENα is a potential target in antitumor immunotherapy.
Project description:we report that USP9X and FBXW11 selectively regulate the stability of PTENα/β but not PTEN proteins by deubiqitination and ubiquitination respectively. USP9X promotes and FBXW11 suppresses tumorigenesis mediated by PTENα/β. In contrast to the current paradigm for PTEN as a tumor suppressor, PTENα/β promote tumorigenesis of cancer cells in a phosphatase-independent manner. Mechanistically, PTENα/β localized in the nucleus regulate expressions of tumor-promoting genes such as NOTCH3 in the similar way as the H3K4 presenter WDR5. Further, PTENα/β but not PTEN directly interact with WDR5 to promote trimethylation of H3K4 and maintain a tumor-promoting signature.
Project description:we report that USP9X and FBXW11 selectively regulate the stability of PTENα/β but not PTEN proteins by deubiqitination and ubiquitination respectively. USP9X promotes and FBXW11 suppresses tumorigenesis mediated by PTENα/β. In contrast to the current paradigm for PTEN as a tumor suppressor, PTENα/β promote tumorigenesis of cancer cells in a phosphatase-independent manner. Mechanistically, PTENα/β localized in the nucleus regulate expressions of tumor-promoting genes such as NOTCH3 in the similar way as the H3K4 presenter WDR5. Further, PTENα/β but not PTEN directly interact with WDR5 to promote trimethylation of H3K4 and maintain a tumor-promoting signature.
Project description:To determine whether PTENα directly binds to viral RNA, we performed Cross-Linking and Immunoprecipitation (CLIP) sequencing of HEK293T cells transfected with vector encoding PTENα under VSV (vesicular stomatitis virus) infection
Project description:Investigation of whole genome gene expression level changes in the liver tissue from LPS/GalN treated mice, compared to LPS treated mice Treatment of mice with LPS and the liver-specific transcriptional inhibitor D-(+)-galactosamine (GalN) induces fatal hepatitis, which is mediated by TNFα and characterized by massive hepatic apoptosis. Previous studies suggest that GalN increases the sensitivity to LPS/TNFα probably by blocking the transcription of protective factors, but the identity of most of these factors is still unclear. This analysis is performed to indentify these protective factors.
Project description:WT immortorized mouse macrophages and CISPR CAS 9 mediated Myristoylated, Alanine-rich C-kinase Substrate knockout ΔMARCKS were treated with LPS for 1h, 6h, 24h. No treatment both WT and ΔMARCKS were use as a control experiment. The label free quantification were prefromed using