PS-341 down-regulates the expression of several proteins involved in DNA repair.

(A) Transcriptional profile detected by oligonucleotide-microarray analysis in MM-1S cells treated with PS-341. Transcriptional changes induced by PS-341 (100 nM, 1-8 hours) included down-regulation of a functional cluster of molecules implicated in the response to genotoxic stress. Color saturation is proportional to magnitude of the difference from the respective control. (B-C) Proteomic analysis of the signaling state of PS-341–treated MM-1S cells. Proteomic analysis detects down-regulation of DNA-PK following 8-hour incubation with PS-341 (as depicted by respective arrows). (D) Immunoblotting confirms that PS-341 decreases protein expression of Ku 80 and Ku 70.