ZIC2-dependent transcriptional regulation is mediated by DNA-dependent protein kinase, poly(ADP-ribose) polymerase, and RNA helicase A

Akira Ishiguro, Maki Ideta, Katsuhiko Mikoshiba, David J. Chen, Jun Aruga

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

The Zic family of zinc finger proteins is essential for animal development, as demonstrated by the holoprosencephaly caused by mammalian Zic2 mutation. To determine the molecular mechanism of Zic-mediated developmental control, we characterized two types of high molecular weight complexes, including Zic2. Complex I was composed of DNA-dependent protein kinase catalytic subunit (DNA-PKcs), Ku70/80, and poly(ADP-ribose) polymerase; complex II contained Ku70/80 and RNA helicase A; all the components interacted directly with Zic2 protein. Immunoprecipitation, subnuclear localization, and in vitro phosphorylation analyses revealed that the DNA-PKcs in complex I played an essential role in the assembly of complex II. Stepwise exchange from complex I to complex II depended on phosphorylation of Zic2 by DNA-PK and poly-(ADP-ribose) polymerase. Phosphorylated Zic2 protein made a stable complex with RNA helicase A, and complex II could interact with RNA polymerase II. Phosphorylation-dependent transformation of Zic2-containing molecular complexes may occur in transcriptional regulation.

Original languageEnglish (US)
Pages (from-to)9983-9995
Number of pages13
JournalJournal of Biological Chemistry
Volume282
Issue number13
DOIs
StatePublished - Mar 30 2007

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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