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

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1795-1803
Number of pages9
JournalCellular Signalling
Volume20
Issue number10
DOIs
Publication statusPublished - 01-10-2008
Externally publishedYes

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Sp1 Transcription Factor
DNA Damage
Phosphorylation
Hydroxyurea
Ionizing Radiation
Confocal Microscopy
Double-Stranded DNA Breaks
DNA Repair
Small Interfering RNA

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Iwahori, Satoko ; Yasui, Yoshihiro ; Kudoh, Ayumi ; Sato, Yoshitaka ; Nakayama, Sanae ; Murata, Takayuki ; Isomura, Hiroki ; Tsurumi, Tatsuya. / Identification of phosphorylation sites on transcription factor Sp1 in response to DNA damage and its accumulation at damaged sites. In: Cellular Signalling. 2008 ; Vol. 20, No. 10. pp. 1795-1803.
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Identification of phosphorylation sites on transcription factor Sp1 in response to DNA damage and its accumulation at damaged sites. / Iwahori, Satoko; Yasui, Yoshihiro; Kudoh, Ayumi; Sato, Yoshitaka; Nakayama, Sanae; Murata, Takayuki; Isomura, Hiroki; Tsurumi, Tatsuya.

In: Cellular Signalling, Vol. 20, No. 10, 01.10.2008, p. 1795-1803.

Research output: Contribution to journalArticle

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