Small Kinetochore Associated Protein (SKAP) Promotes UV-Induced Cell Apoptosis through Negatively Regulating Pre-mRNA Processing Factor 19 (Prp19)

• DOI: 10.1371/journal.pone.0092712
• Publication Date: 2014-04-09T20:36:20Z
• Authors: Shan Lu; Renxian Wang; Congli Cai; Junbo Liang; Longchang Xu; Shiying Miao; Linfang Wang; Wei Song
• Keywords: 0301 basic medicine; Ultraviolet Rays; Science; Molecular Sequence Data; Apoptosis; Cell Cycle Proteins; Chromatography, Affinity; Mass Spectrometry; Cell Line; Evolution, Molecular; 03 medical and health sciences; Humans; Amino Acid Sequence; Gene Silencing; Conserved Sequence; Q; R; Nuclear Proteins; DNA Repair Enzymes; Gene Knockdown Techniques; Medicine; RNA Splicing Factors; Microtubule-Associated Proteins; Research Article; Protein Binding

Apoptosis is a regulated cellular suicide program that is critical for the development and maintenance of healthy tissues. Previous studies have shown that small kinetochore associated protein (SKAP) cooperates with kinetochore and mitotic spindle proteins to regulate mitosis. However, the role of SKAP in apoptosis has not been investigated. We have identified a new interaction involving SKAP, and we propose a mechanism through which SKAP regulates cell apoptosis. Our experiments demonstrate that both overexpression and knockdown of SKAP sensitize cells to UV-induced apoptosis. Further study has revealed that SKAP interacts with Pre-mRNA processing Factor 19 (Prp19). We find that UV-induced apoptosis can be inhibited by ectopic expression of Prp19, whereas silencing Prp19 has the opposite effect. Additionally, SKAP negatively regulates the protein levels of Prp19, whereas Prp19 does not alter SKAP expression. Finally, rescue experiments demonstrate that the pro-apoptotic role of SKAP is executed through Prp19. Taken together, these findings suggest that SKAP promotes UV-induced cell apoptosis by negatively regulating the anti-apoptotic protein Prp19.