Identification of phosphorylation sites on transcription factor Sp1 in response to DNA damage and its accumulation at damaged sites

Satoko Iwahori, Yoshihiro Yasui, Ayumi Kudoh, Yoshitaka Sato, Sanae Nakayama, Takayuki Murata, Hiroki Isomura, Tatsuya Tsurumi

研究成果: Article査読

49 被引用数 (Scopus)

抄録

DNA damage induces hyper-phosphorylation of the Sp1 transcriptional factor. We have demonstrated that ionizing radiation-associated DNA double-strand breaks (DSBs) induce phosphorylation of at least Ser-56 and Ser-101 residues on Sp1 in an ATM-dependent manner. UV irradiation- or hydroxyurea (HU)-induced replicative stress results in phosphorylation of only the Ser-101 residue. Furthermore, silencing of the ATM- and Rad3-related protein (ATR) in ATM-deficient cells treated with HU abrogated the Ser-101 phosphorylation. Thus, phosphorylation of Ser-101 on Sp1 appears to be a general response to DNA damage dependent on both ATM and ATR. Although silencing of Sp1 expression by siRNA targeting resulted in an increase in sensitivity to ionizing radiation (IR), the Ser-101 phosphorylation did not affect transcriptional activity from the Sp1 responsive promoter. Confocal laser microscopy analysis revealed co-localization of phosphorylated Sp1 at Ser-101 with phosphorylated ATM at Ser-1981, the affected sites representing DSBs. These observations suggest that phosphorylated Sp1 might play a role in DNA repair at damage sites rather than functioning in transcriptional regulation.

本文言語English
ページ(範囲)1795-1803
ページ数9
ジャーナルCellular Signalling
20
10
DOI
出版ステータスPublished - 10-2008
外部発表はい

All Science Journal Classification (ASJC) codes

  • 細胞生物学

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