Small kinetochore associated protein (SKAP) promotes UV-induced cell apoptosis through negatively regulating pre-mRNA processing factor 19 (Prp19).
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.
State Key Laboratory of Medical Molecular Biology, Dept. of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
Shan
S
Lu
State Key Laboratory of Medical Molecular Biology, Dept. of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
Renxian
R
Wang
State Key Laboratory of Medical Molecular Biology, Dept. of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
Congli
C
Cai
State Key Laboratory of Medical Molecular Biology, Dept. of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
Junbo
J
Liang
State Key Laboratory of Medical Molecular Biology, Dept. of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
Longchang
L
Xu
State Key Laboratory of Medical Molecular Biology, Dept. of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
Shiying
S
Miao
State Key Laboratory of Medical Molecular Biology, Dept. of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
Linfang
L
Wang
State Key Laboratory of Medical Molecular Biology, Dept. of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
Wei
W
Song
D000595:Amino Acid Sequence; D017209:Apoptosis / Q000528:radiation effects*; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D002846:Chromatography, Affinity; D017124:Conserved Sequence; D045643:DNA Repair Enzymes / Q000235:genetics* / Q000378:metabolism; D019143:Evolution, Molecular; D055785:Gene Knockdown Techniques; D020868:Gene Silencing / Q000528:radiation effects; D006801:Humans; D013058:Mass Spectrometry; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding / Q000528:radiation effects; D000072260:RNA Splicing Factors; D014466:Ultraviolet Rays
D018797:Cell Cycle Proteins; C555984:KNSTRN protein, human; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D000072260:RNA Splicing Factors; D045643:DNA Repair Enzymes; C417041:PRPF19 protein, human