A novel GDNF-inducible gene, BMZF3, encodes a transcriptional repressor associated with KAP-1.
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.
Department of Pathology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8850, Japan.
Chikage
C
Suzuki
Yoshiki
Y
Murakumo
Yukari
Y
Kawase
Tomoko
T
Sato
Takatoshi
T
Morinaga
Naoyuki
N
Fukuda
Atsushi
A
Enomoto
Masatoshi
M
Ichihara
Masahide
M
Takahashi
D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology*; D000076183:Tripartite Motif-Containing Protein 28
D004268:DNA-Binding Proteins; D051100:Glial Cell Line-Derived Neurotrophic Factor; D012097:Repressor Proteins; C526280:ZNF256 protein, human; C101116:TRIM28 protein, human; D000076183:Tripartite Motif-Containing Protein 28