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Small kinetochore associated protein (SKAP) promotes UV-induced cell apoptosis through negatively regulating pre-mRNA
Shan Lu1, Renxian Wang1, Congli Cai1
1State 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.
Abstract:
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.
Insights
Small kinetochore associated protein (SKAP) promotes UV-induced apoptosis by regulating the anti-apoptotic protein Pre-mRNA processing Factor 19 (Prp19). SKAP
Area of Science:
- Cell biology
- Molecular biology
- Biochemistry
Background:
- Apoptosis is a crucial cellular process for tissue homeostasis.
- Small kinetochore associated protein (SKAP) is known to regulate mitosis.
- The role of SKAP in apoptosis remains unexplored.
Purpose of the Study:
- To investigate the role of SKAP in apoptosis.
- To elucidate the mechanism by which SKAP regulates cell death.
- To identify novel SKAP-interacting proteins involved in apoptosis.
Main Methods:
- Overexpression and knockdown of SKAP in cells.
- UV irradiation to induce apoptosis.
- Co-immunoprecipitation to detect protein interactions.
- Western blotting to assess protein levels.
- Rescue experiments to validate functional pathways.
Main Results:
- Both SKAP overexpression and knockdown sensitize cells to UV-induced apoptosis.
- SKAP interacts with Pre-mRNA processing Factor 19 (Prp19).
- Prp19 inhibits UV-induced apoptosis, while Prp19 silencing enhances it.
- SKAP negatively regulates Prp19 protein levels.
- The pro-apoptotic effect of SKAP is mediated through Prp19.
Conclusions:
- SKAP promotes UV-induced apoptosis.
- SKAP exerts its pro-apoptotic function by negatively regulating the anti-apoptotic protein Prp19.
- This study reveals a novel mechanism of apoptosis regulation involving SKAP and Prp19.
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