Sonic Hedgehog signaling impairs ionizing radiation-induced checkpoint activation and induces genomic instability.
Sonic Hedgehog signaling impairs ionizing radiation-induced checkpoint activation and induces genomic instability.
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DOI：
10.1083/jcb.200804042
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发表时间：
2008-11-03
期刊：
影响因子：
--
通讯作者：
Karnitz LM
中科院分区：
文献类型：
--
作者：
Leonard JM;Ye H;Wetmore C;Karnitz LM
The Sonic Hedgehog (Shh) pathway plays important roles in embryogenesis, stem cell maintenance, tissue repair, and tumorigenesis. Haploinsufficiency of Patched-1, a gene that encodes a repressor of the Shh pathway, dysregulates the Shh pathway and increases genomic instability and the development of spontaneous and ionizing radiation (IR)–induced tumors by an unknown mechanism. Here we show that Ptc1+/− mice have a defect in the IR-induced activation of the ATR–Chk1 checkpoint signaling pathway. Likewise, transient expression of Gli1, a downstream target of Shh signaling, disrupts Chk1 activation in human cells by preventing the interaction of Chk1 with Claspin, a Chk1 adaptor protein that is required for Chk1 activation. These results suggest that inappropriate Shh pathway activation promotes tumorigenesis by disabling a key signaling pathway that helps maintain genomic stability and inhibits tumorigenesis.
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影响因子：
64.8
作者：
Bartkova, J;Horejsi, Z;Bartek, J
通讯作者：
Bartek, J
影响因子：
8
作者：
Pazzaglia, S;Tanori, M;Saran, A
通讯作者：
Saran, A
影响因子：
8
作者：
Durkin, S. G.;Arlt, M. F.;Glover, T. W.
通讯作者：
Glover, T. W.
影响因子：
21.3
作者：
Jazayeri, A;Falck, J;Jackson, SP
通讯作者：
Jackson, SP
DOI：
10.1083/jcb.200211048
发表时间：
2003-02-03
期刊：
The Journal of cell biology
影响因子：
--
作者：
Babu JR;Jeganathan KB;Baker DJ;Wu X;Kang-Decker N;van Deursen JM
通讯作者：
van Deursen JM