ZIP: a novel transcription repressor, represses EGFR oncogene and suppresses breast carcinogenesis.
Despite the importance of epidermal growth factor receptor (EGFR) in animal development and malignant transformation, surprisingly little is known about the regulation of its expression. Here, we report a novel zinc finger and G-patch domain-containing protein, ZIP. We demonstrated that ZIP acts as a transcription repressor through the recruitment of the nucleosome remodelling and deacetylase complex. Transcriptional target analysis revealed that ZIP regulates several cellular signalling pathways including EGFR pathways that are critically involved in cell proliferation, survival, and migration. We showed that ZIP inhibits cell proliferation and suppresses breast carcinogenesis, and that ZIP depletion leads to a drastic tumour growth in vivo. We found that ZIP is downregulated in breast carcinomas and that its level of expression is negatively correlated with that of EGFR. Our data indicate that ZIP is a novel transcription repressor and a potential tumour suppressor. These findings may shed new light on the EGFR-related breast carcinogenesis and might offer a potential new target for breast cancer therapy.
Li
Ruifang
R
Department of Biochemistry and Molecular Biology, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Health Science Center, Beijing, China.
Zhang
Hua
H
Yu
Wenhua
W
Chen
Yupeng
Y
Gui
Bin
B
Liang
Jing
J
Wang
Yan
Y
Sun
Luyang
L
Yang
Xiaohan
X
Zhang
Yu
Y
Shi
Lei
L
Li
Yanyan
Y
Shang
Yongfeng
Y
D000595:Amino Acid Sequence; D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015674:Mammary Neoplasms, Animal / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009707:Nucleosomes / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D027682:Cation Transport Proteins; D009707:Nucleosomes; C403517:SLC39A1 protein, human; D066246:ErbB Receptors