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Phosphorylation of Sp1 in response to DNA damage by ataxia telangiectasia-mutated kinase
Journal article   Open access   Peer reviewed

Phosphorylation of Sp1 in response to DNA damage by ataxia telangiectasia-mutated kinase

Beatrix A Olofsson, Crystal M Kelly, Jiyoon Kim, Stephen M Hornsby and Jane Azizkhan-Clifford
Molecular cancer research, v 5(12), pp 1319-1330
Dec 2007
DOI: https://doi.org/10.1158/1541-7786.MCR-07-0374
PMID: 18171990
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1158/1541-7786.MCR-07-0374View
Published, Version of Record (VoR) Open

Abstract

Amino Acid Sequence Cell Line Oxidants - pharmacology Tumor Suppressor Proteins - metabolism Mutagenesis, Site-Directed Fibroblasts - physiology Humans Cell Cycle Proteins - metabolism Hydrogen Peroxide - pharmacology Protein-Serine-Threonine Kinases - genetics Molecular Sequence Data Substrate Specificity Sp1 Transcription Factor - metabolism Ataxia Telangiectasia Mutated Proteins DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Sp1 Transcription Factor - genetics Tumor Suppressor Proteins - genetics Cell Cycle Proteins - genetics Fibroblasts - cytology DNA Damage Phosphorylation - drug effects Cell Survival - physiology Protein-Serine-Threonine Kinases - metabolism
Sp1, a transcription factor that regulates expression of a wide array of essential genes, contains two SQ/TQ cluster domains, which are characteristic of ATM kinase substrates. ATM substrates are transducers and effectors of the DNA damage response, which involves sensing damage, checkpoint activation, DNA repair, and/or apoptosis. A role for Sp1 in the DNA damage response is supported by our findings: Activation of ATM induces Sp1 phosphorylation with kinetics similar to H2AX; inhibition of ATM activity blocks Sp1 phosphorylation; depletion of Sp1 sensitizes cells to DNA damage and increases the frequency of double strand breaks. We have identified serine 101 as a critical site phosphorylated by ATM; Sp1 with serine 101 mutated to alanine (S101A) is not significantly phosphorylated in response to damage and cannot restore increased sensitivity to DNA damage of cells depleted of Sp1. Together, these data show that Sp1 is a novel ATM substrate that plays a role in the cellular response to DNA damage.

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Web of Science research areas
Cell Biology
Oncology
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