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

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• 作者：Chikage Suzuki ; Yoshiki Murakumo ; Yukari Kawase ; Tomoko Sato ; Takatoshi Morinaga ; Naoyuki Fukuda ; Atsushi Enomoto ; Masatoshi Ichihara ; Masahide Takahashi
• 关键词：BMZF3 ; GDNF-inducible gene ; KRAB-zinc finger ; Transcriptional repressor ; KAP-1
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2008
• 出版时间：1 February 2008
• 年：2008
• 卷：366
• 期：1
• 页码：226-232
• 全文大小：279 K

文摘

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 1 h 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.