Rpp40 Inhibitors

Chemical inhibitors of Rpp40 can be categorized based on the specific stages of gene expression they target, thereby leading to inhibition of Rpp40 activity. Alsterpaullone targets the cell cycle by inhibiting cyclin-dependent kinases, leading to potential alterations in the processing and maturation of ribosomal RNA, activities central to the function of Rpp40. Actinomycin D directly binds to DNA, preventing transcription of RNA, which Rpp40 processes. Harringtonine and Homoharringtonine disrupt protein biosynthesis during translation elongation and the establishment of the initial peptide chain, respectively. This disruption can lead to a reduction in the availability of proteins necessary for Rpp40's function or its regulatory processes, thereby inhibiting the protein's activity. Pladienolide B binds to the SF3b complex, inhibiting splicing, which can disrupt pre-RNA processing and maturation involving Rpp40.

Furthermore, Silvestrol and Rocaglamide, both eIF4A inhibitors, reduce the synthesis of proteins, which could include those that interact with or regulate Rpp40. CX-5461 inhibits RNA Polymerase I, reducing ribosomal RNA synthesis, thereby likely inhibiting Rpp40's function given its role in rRNA processing. Triptolide decreases the levels of RNAs and proteins by inhibiting RNA Polymerase II, reducing substrates required for Rpp40's ribonuclease activity. Tunicamycin inhibits N-linked glycosylation, affecting proteins and pathways that may regulate Rpp40. Mycalamide A inhibits overall protein synthesis, which can lead to a reduction in proteins that Rpp40 processes or that regulate its activity. Lastly, Cycloheximide interferes with the translocation step in protein synthesis, which would inhibit Rpp40's function by limiting the availability of interacting or regulatory proteins. Each chemical, through its unique mode of action, ultimately leads to an inhibition of Rpp40's role in RNA processing.