IndraLab

"Indeed, zebrafish expressing a hypomorphic SF3B1 xref gene or truncated PRPF8 xref demonstrate selective defects in neural crest development and neuronal apoptosis, respectively, while constitutional PRPF8 -inactivating mutations in humans are causative of retinitis pigmentosa, a disease of the neural crest-derived retina. xref However, a genome-scale siRNA knockdown screen using multiple myeloma, a hematolymphoid tumor with an Mcl1 survival dependence, xref also identified three splicing components ( PRPF8 , SF3A1 and SNRPA1 ) as demonstrating selective lethality, and spliceosome components were the only hits with higher activity than Mcl1 knockdown itself. xref In this study, seven proteasome targets were also identified (though not PSMD14 ) supporting that, while the specific regulatory proteins identified may differ across cancer types, the core regulatory pathways may be conserved in Mcl1-dependent cancers."