Stephania tetrandra
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA690643 | ENA |
REPOSITORIES: ENA
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Project description:Tetrandrine (Tet), a bis-benzylisoquinoline alkaloid isolated from Stephania tetrandra, has been implicated in a broad range of pharmacological activities, and is best known for its highly potent activity against Ebola virus infection by inhibiting NAADP-mediated calcium release via the endosomal/lysosomal two-pore channels (TPCs). It has been proposed that Tet inhibits the activity of TPCs directly, despite a lack of direct evidence. Using a synthetic, alkynyl diazirine derivative of Tet (AD-Tet), a clickable photoaffinity probe as a tool for target identification, we present results from pulldown SILAC-MS, transcriptomics, biochemical and cell analysis to show that Tet/AD-Tet specifically targets lysosomal integral membrane protein-2 (LIMP-2), a lysosomal cholesterol transporter. Accordingly, we delineated the principles underlying the autophagic and cytotoxic properties of Tet, and discovered that hypercholesteremia is a previously unknown side-effect of Tet in vivo. More importantly, we discover that LIMP-2 is an essential regulator of NAADP-mediated calcium release, and implies that LIMP-2 is a novel target for the development of anti-Ebola virus therapeutics.
2023-03-04 | GSE212648 | GEO
Project description:Purpose: We conducted a reverse genetic approach in order to elucidate the role of H3K27me3 writers and erasers in the process of sex determination and expression in melon. Methods: We used TILLING to find loss-of function mutants of cmLHP1 proteins in melon. Selected alleles were phenotyped at the developmental and molecular levels. We generated the cmlhp1ab mutant, for which we observed a pleiotropic phenotype. For this double mutant, we integrated RNA-seq (leaves), ChIP-seq (leaves) and RT-PCR (flowers) for elucidating the impact of cmLHP1 loss of function at the molecular level. Results: cmlhp1ab displayed a pleiotropic phenotype which correlated with genome-wide changes of H3K27me3 (moore oftenly hypomethylation) and deregulation of genes involved in flower development and hormone responses.
2022-02-15 | GSE180385 | GEO