A novel GDNF-inducible gene, BMZF3, encodes a transcriptional repressor associated with KAP-1.

Chikage Suzuki, Yoshiki Murakumo, Yukari Kawase, Tomoko Sato, Takatoshi Morinaga, Naoyuki Fukuda, Atsushi Enomoto, Masatoshi Ichihara, Masahide Takahashi

Department of Pathology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8850, Japan.

Biochemical and biophysical research communications 2008 Feb 1

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The Krüppel-associated box (KRAB)-containing zinc finger proteins (ZFPs) comprise the largest family of zinc finger transcription factors that function as transcriptional repressors. In the study of glial cell line-derived neurotrophic factor (GDNF)-RET signaling, we have identified bone marrow zinc finger 3 (BMZF3), encoding a KRAB-ZFP, as a GDNF-inducible gene by differential display analysis. The expression of BMZF3 transcripts in the human neuroblastoma cell line TGW increased 1h after GDNF stimulation, as determined by Northern blotting and quantitative reverse-transcriptase polymerase chain reaction. The BMZF3 possesses transcriptional repressor activity in the KRAB domain. BMZF3 interacts with a co-repressor protein, KRAB-associated protein 1 (KAP-1), through the KRAB domain and siRNA-mediated knockdown of KAP-1 abolished the transcriptional repressor activity of BMZF3, indicating that KAP-1 is necessary for BMZF3 function. Furthermore, siRNA-mediated silencing of BMZF3 inhibited cell proliferation. These findings suggest that BMZF3 is a transcriptional repressor induced by GDNF that plays a role in cell proliferation.

Citation

Chikage Suzuki, Yoshiki Murakumo, Yukari Kawase, Tomoko Sato, Takatoshi Morinaga, Naoyuki Fukuda, Atsushi Enomoto, Masatoshi Ichihara, Masahide Takahashi. A novel GDNF-inducible gene, BMZF3, encodes a transcriptional repressor associated with KAP-1. Biochemical and biophysical research communications. 2008 Feb 1;366(1):226-32