Publication: Autophosphorylation and Pin1 binding coordinate DNA damage-induced HIPK2 activation and cell death
Autophosphorylation and Pin1 binding coordinate DNA damage-induced HIPK2 activation and cell death
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Bitomsky, N., Conrad, E., Moritz, C., Polonio-Vallon, T., Sombroek, D., Schultheiss, K., Glas, C., Greiner, V., Herbel, C., Mantovani, F., del Sal, G., Peri, F., & Hofmann, T. G. (2013). Autophosphorylation and Pin1 binding coordinate DNA damage-induced HIPK2 activation and cell death. Proceedings of the National Academy of Sciences of the United States of America, 110(45), E4203–E4212. https://doi.org/10.1073/pnas.1310001110
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Excessive genome damage activates the apoptosis response. Protein kinase HIPK2 is a key regulator of DNA damage-induced apoptosis. Here, we deciphered the molecular mechanism of HIPK2 activation and show its relevance for DNA damage-induced apoptosis in cellulo and in vivo. HIPK2 autointeracts and site-specifically autophosphorylates upon DNA damage at Thr880/Ser882. Autophosphorylation regulates HIPK2 activity and mutation of the phosphorylation-acceptor sites deregulates p53 Ser46 phosphorylation and apoptosis in cellulo. Moreover,
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- Bitomsky, N
- Conrad, E
- Moritz, C
- Polonio-Vallon, T
- Sombroek, D
- Schultheiss, K
- Glas, C
- Greiner, V
- Herbel, C
- Mantovani, F
- del Sal, G
- Peri, F
- Hofmann, T G
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Bitomsky, N., Conrad, E., Moritz, C., Polonio-Vallon, T., Sombroek, D., Schultheiss, K., Glas, C., Greiner, V., Herbel, C., Mantovani, F., del Sal, G., Peri, F., & Hofmann, T. G. (2013). Autophosphorylation and Pin1 binding coordinate DNA damage-induced HIPK2 activation and cell death. Proceedings of the National Academy of Sciences of the United States of America, 110(45), E4203–E4212. https://doi.org/10.1073/pnas.1310001110