The cAMP signaling system inhibits the repair of γ-ray-induced DNA damage by promoting Epac1-mediated proteasomal degradation of XRCC1 protein in human lung cancer cells

Biochemical and Biophysical Research Communications
Eun-Ah Cho, Yong-Sung Juhnn

Abstract

Cyclic AMP is involved in the regulation of metabolism, gene expression, cellular growth and proliferation. Recently, the cAMP signaling system was found to modulate DNA-damaging agent-induced apoptosis by regulating the expression of Bcl-2 family proteins and inhibitors of apoptosis. Thus, we hypothesized that the cAMP signaling may modulate DNA repair activity, and we investigated the effects of the cAMP signaling system on γ-ray-induced DNA damage repair in lung cancer cells. Transient expression of a constitutively active mutant of stimulatory G protein (GαsQL) or treatment with forskolin, an adenylyl cyclase activator, augmented radiation-induced DNA damage and inhibited repair of the damage in H1299 lung cancer cells. Expression of GαsQL or treatment with forskolin or isoproterenol inhibited the radiation-induced expression of the XRCC1 protein, and exogenous expression of XRCC1 abolished the DNA repair-inhibiting effect of forskolin. Forskolin treatment promoted the ubiquitin and proteasome-dependent degradation of the XRCC1 protein, resulting in a significant decrease in the half-life of the protein after γ-ray irradiation. The effect of forskolin on XRCC1 expression was not inhibited by PKA inhibitor, but 8-pCPT-2'-O-M...Continue Reading

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Citations

Sep 27, 2014·Biochimica Et Biophysica Acta·Avinash AppukuttanYury Ladilov
Feb 9, 2018·Molecular and Cellular Biochemistry·Naveen KumarSeema Sehrawat
Sep 10, 2020·International Journal of Molecular Sciences·Nadine WehbeElias Baydoun
Aug 29, 2020·Cells·Karina FormosoJeanne Mialet-Perez
Jul 17, 2020·The Journal of Clinical Investigation·Anat Ben-ShlomoShlomo Melmed

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