ZNF383, a novel KRAB-containing zinc finger protein, suppresses MAPK signaling pathway.
Mitogen-activated protein kinases (MAPKs) are major components of pathways controlling embryogenesis, cell differentiation, cell proliferation, and cell death. One of the most explored functions of MAPK signaling is the regulation of gene expression by direct or indirect phosphorylation and subsequent activation of transcription factors. In this article, we isolated a novel KRAB-related zinc finger gene named ZNF383 from an early embryo heart cDNA library. The cDNA of ZNF383 is 2220bp, encoding a protein of 475 amino acids. The protein is conserved in evolution across different species. Northern blot analysis indicates that a 2.2kb transcript specific for ZNF383 is detected in most of the examined human adult and embryonic tissues with a higher level in skeletal muscle. In COS-7 cells, ZNF383 protein is localized to nucleus and cytoplasm. ZNF383 is a transcription repressor when fused to Gal-4 DNA-binding domain and cotransfected with VP-16. Deletion analysis indicates that the KRAB box of ZNF383 is responsible for the transcriptional repressor activity. Overexpression of ZNF383 in cells inhibits the transcriptional activities of AP-1 and SRE, suggesting that ZNF383 may act as a negative regulator in MAPK-mediated signaling pathways.
Cao
Lei
L
The Center for Heart Development, College of Life Sciences, Hunan Normal University, Changsha, 410081 Hunan, People's Republic of China.
Wang
Zhi
Z
Zhu
Chuanbing
C
Zhao
Yulian
Y
Yuan
Wuzhou
W
Li
Jing
J
Wang
Yuequn
Y
Ying
Zhaochu
Z
Li
Yongqing
Y
Yu
Weishi
W
Wu
Xiushan
X
Liu
Mingyao
M
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006321:Heart / Q000196:embryology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism*; D009928:Organ Specificity; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D014018:Tissue Distribution; D016335:Zinc Fingers / Q000502:physiology*
D004268:DNA-Binding Proteins; D012097:Repressor Proteins; C422407:ZNF350 protein, human; C503413:ZNF383 protein, human