Overlaid Transcriptional and Proteome Analyses Identify Mitotic Kinesins as Important Targets of Arylsulfonamide-Mediated RBM39 Degradation.

ABSTRACT: Certain arylsulfonamides (ArSulf) induce an interaction between the E3 ligase substrate adaptor DCAF15 and the critical splicing factor RBM39, ultimately causing its degradation. However, degradation of a splicing factor introduces complex pleiotropic effects that are difficult to untangle, since, aside from direct protein degradation, downstream transcriptional effects also influence the proteome. By overlaying transcriptional data and proteome datasets, we distinguish transcriptional from direct degradation effects, pinpointing those proteins most impacted by splicing changes. Using our workflow, we identify and validate the upregulation of the arginine-and-serine rich protein (RSRP1) and the downregulation of the key kinesin motor proteins KIF20A and KIF20B due to altered splicing in th

SUBMITTER: Coomar S 

PROVIDER: S-EPMC10395616 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature