期刊
MOLECULAR AND CELLULAR BIOLOGY
卷 23, 期 21, 页码 7510-7524出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.23.21.7510-7524.2003
关键词
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资金
- NCI NIH HHS [R01CA095518-01, R01CA89052, R01 CA089052, R01 CA095518] Funding Source: Medline
- NINDS NIH HHS [P01 NS36466-06, P01 NS036466] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [R01CA095518, R01CA089052] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [P01NS036466] Funding Source: NIH RePORTER
The receptor for insulin-like growth factor I (IGF-IR) controls normal and pathological growth of cells. DNA repair pathways represent an unexplored target through which the IGF-IR signaling system might support pathological growth leading to cellular transformation. However, this study demonstrates that IGF-I stimulation supports homologous recombination-directed DNA repair (HRR). This effect involves an interaction between Rad51 and the major IGF-IR signaling molecule, insulin receptor substrate 1 (IRS-1). The binding occurs within the cytoplasm, engages the N-terminal domain of IRS-1, and is attenuated by IGF-1-mediated IRS-1 tyrosine phosphorylation. In the absence of IGF-I stimulation, or if mutated IGF-IR fails to phosphorylate IRS-1, localization of Rad51 to the sites of damaged DNA is diminished. These results point to a direct role of IRS-1 in HRR and suggest a novel role for the IGF-IR/IRS-1 axis in supporting the stability of the genome.
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