Ciz is a zinc finger transcription factor with nucleocytoplasmic shuttling activity. Ciz-deficient mice show high bone mass phenotype. As a first step to address how Ciz suppresses bone formation, we examined the binding partners of Ciz based on a yeast two-hybrid screening. While Ciz is an intracellular protein, 47% of the positive clones were genes encoding extracellular matrix proteins, including Colla1, Colla2, FbIn2, and Rpsa. In vitro coimmunoprecipitation experiments using in vitro translated proteins revealed direct binding of Ciz-Delta ZF (zinc finger) to C-propeptides of and Colla2. In vivo association of the transfected Ciz and C-propeptide of Colla1 was observed in COS-7 cells based on immunoprecipitation. In terms of intracellular localization, overexpressed C-propeptides of Coll and Ciz were co-localized in nuclei. These results revealed that Ciz interacts with C-propeptides of type I collagen and this association takes place in nuclei. (C) 2008 Elsevier Inc. All rights reserved.