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Oxaboroles target trypanosome CPSF3 - Acoziborole screen

ABSTRACT: Oxaboroles target trypanosome CPSF3 - Acoziborole screen

PROVIDER: PRJEB25884 | ENA |

REPOSITORIES: ENA

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Oxaboroles target trypanosome CPSF3

Project description:Oxaboroles target trypanosome CPSF3 - DDD85646 screen

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Oxaboroles target trypanosome CPSF3

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CPSF3 inhibition blocks pancreatic cancer cell proliferation through disruption of core histone mRNA processing

Project description:Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with limited effective treatment options, potentiating the importance of uncovering novel drug targets. Here, we target Cleavage and Polyadenylation Specificity Factor 3 (CPSF3), the 3’ endonuclease that catalyzes mRNA cleavage during polyadenylation and histone mRNA processing. We find that CPSF3 is highly expressed in PDAC and is associated with poor prognosis. CPSF3 knockdown blocks PDAC cell proliferation and colony formation in vitro and tumor growth in vivo. Chemical inhibition of CPSF3 by the small molecule JTE-607 also attenuates PDAC cell proliferation and colony formation, while it has no effect on cell proliferation of non-transformed immortalized control pancreatic cells. Mechanistically, JTE-607 induces transcriptional read-through in replication-dependent histones, reduces core histone expression, destabilizes chromatin structure and arrests cells in the S-phase of the cell cycle. Therefore, CPSF3 represents a potential therapeutic target for the treatment of PDAC.

2024-01-06 | GSE252667 | GEO

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Clinical and veterinary trypanocidal benzoxaboroles target CPSF3.

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Target identification of an antimalarial oxaborole identifies AN13762 as an alternative chemotype for targeting CPSF3 in apicomplexan parasites.

Project description:Target identification of an antimalarial oxaborole identifies AN13762 as an alternative chemotype for targeting CPSF3 in apicomplexan parasites.

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Project description:The roles of 3’-exoribonucleases and the exosome in trypanosome mRNA degradation; 30 min after actinomycin D +sinefungin, RNAi against CAf1, CNOT10, PAN2. These are really old data that hadn't been deposited.The datasets called RNA1, RNA2, RNA3 and RNA4 are almost certainly, from their location in the folder and from new alignment results, from the RRP45 RNAi.

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