Negative regulation of bone morphogenetic protein/Smad signaling by Cas-interacting zinc finger protein in osteoblasts.

Zhong Jian Shen, Tetsuya Nakamoto, Kunikazu Tsuji, Akira Nifuji, Kohei Miyazono, Toshihisa Komori, Hisamaru Hirai, Masaki Noda

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Bone morphogenetic protein (BMP) signaling regulates body axis determination, apoptosis, and differentiation of various types of cells including neuron, gut, and bone cells. However, the molecules involved in such BMP regulation of biological events have not been fully understood. Here, we examined the involvement of Cas-interacting zinc finger protein (CIZ) in the modulation of BMP2-induced osteoblastic cell differentiation. CIZ overexpression in osteoblastic MC3T3E1 cells suppressed BMP2-enhanced expression of alkaline phosphatase, osteocalcin, and type I collagen genes. Upstream analyses revealed that CIZ overexpression also suppressed BMP2-induced enhancement of the mRNA expression of Cbfa1, which is a critical transcription factor for osteoblastic differentiation. BMP-induced Smad1 and Smad5 activation of GCCG-mediated transcription was blocked in the presence of CIZ overexpression. CIZ overexpression alone in the absence of BMP2 moderately enhanced basal levels of Cbfa1 mRNA expression. CIZ overexpression also enhanced 1.8-kb Cbfa1 promoter activity in the absence of BMP2, whereas it suppressed the promoter activity in the presence of BMP2. Finally, CIZ overexpression suppressed the formation of mineralized nodules in osteoblastic cell cultures. These data indicate that CIZ is a novel type inhibitor of BMP/Smad signaling.

Original languageEnglish (US)
Pages (from-to)29840-29846
Number of pages7
JournalJournal of Biological Chemistry
Volume277
Issue number33
StatePublished - Aug 16 2002

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Bone Morphogenetic Proteins
Zinc Fingers
Osteoblasts
Zinc
Cell Differentiation
Proteins
Messenger RNA
Osteocalcin
Transcription
Collagen Type I
Cell culture
Neurons
Alkaline Phosphatase
Bone
Transcription Factors
Cell Culture Techniques
Genes
Chemical activation
Modulation
Apoptosis

ASJC Scopus subject areas

  • Biochemistry

Cite this

Shen, Z. J., Nakamoto, T., Tsuji, K., Nifuji, A., Miyazono, K., Komori, T., ... Noda, M. (2002). Negative regulation of bone morphogenetic protein/Smad signaling by Cas-interacting zinc finger protein in osteoblasts. Journal of Biological Chemistry, 277(33), 29840-29846.

Negative regulation of bone morphogenetic protein/Smad signaling by Cas-interacting zinc finger protein in osteoblasts. / Shen, Zhong Jian; Nakamoto, Tetsuya; Tsuji, Kunikazu; Nifuji, Akira; Miyazono, Kohei; Komori, Toshihisa; Hirai, Hisamaru; Noda, Masaki.

In: Journal of Biological Chemistry, Vol. 277, No. 33, 16.08.2002, p. 29840-29846.

Research output: Contribution to journalArticle

Shen, ZJ, Nakamoto, T, Tsuji, K, Nifuji, A, Miyazono, K, Komori, T, Hirai, H & Noda, M 2002, 'Negative regulation of bone morphogenetic protein/Smad signaling by Cas-interacting zinc finger protein in osteoblasts.', Journal of Biological Chemistry, vol. 277, no. 33, pp. 29840-29846.
Shen, Zhong Jian ; Nakamoto, Tetsuya ; Tsuji, Kunikazu ; Nifuji, Akira ; Miyazono, Kohei ; Komori, Toshihisa ; Hirai, Hisamaru ; Noda, Masaki. / Negative regulation of bone morphogenetic protein/Smad signaling by Cas-interacting zinc finger protein in osteoblasts. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 33. pp. 29840-29846.
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