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

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.
Authors	Akira Ishiguro, Maki Ideta, Katsuhiko Mikoshiba, David J Chen, Jun Aruga
Journal	The Journal of biological chemistry (J Biol Chem) Vol. 282 Issue 13 Pg. 9983-9995 (Mar 30 2007) ISSN: 0021-9258 [Print] United States
PMID	17251188 (Publication Type: Journal Article)
Chemical References	Neoplasm Proteins Nuclear Proteins Transcription Factors ZIC2 protein, human Poly(ADP-ribose) Polymerases DNA-Activated Protein Kinase DHX9 protein, human DEAD-box RNA Helicases
Topics	Cell Line DEAD-box RNA Helicases (metabolism, physiology) DNA-Activated Protein Kinase (physiology) Gene Expression Regulation (physiology) Humans Neoplasm Proteins (metabolism, physiology) Nuclear Proteins (metabolism, physiology) Phosphorylation Poly(ADP-ribose) Polymerases (physiology) Transcription Factors (metabolism, physiology) Transcription, Genetic (physiology)

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