Activation of transcriptional activities of AP1 and SRE by a novel zinc finger protein ZNF445.
Zinc finger proteins play important roles in various cellular functions, including cell proliferation, differentiation, and apoptosis. Mitogen-activated protein kinase (MAPK) signal transduction pathways are one of the most common mechanisms in eukaryotic cell regulation. Many transcription factors are important targets of MAPKs. In this study, we identified a novel gene encoding a zinc finger protein named ZNF445. The ZNF445 mRNA consists of 9105 nucleotides and has a 1031-amino acid open reading frame. The predicted 119-kDa protein contains a leucine-rich region (LER or SCAN domain) at the N-terminus, followed by a well-conserved Krüppel-associated box (KRAB) domain. At the C-terminus of the protein, there are 14 C2H2 (Cys2-His2) zinc finger motifs. ZNF445 gene is mapped to chromosome 3p21.32. Northern blot analysis indicates that a 9.1 kb transcript specific for ZNF445 is expressed in uterus, thymus, small intestine, colon, pancreas, peripheral blood leukocyte, and especially at a higher level in the testis and skeletal muscle in human adult tissues. ZNF445 protein was located in the nucleus when overexpressed in cultured cells. Reporter gene assays showed that ZNF445 is a transcriptional repressor, and overexpression of ZNF445 in the HEK 293T cells activates the transcriptional activities of AP1 and SRE. Deletion studies showed that the SCAN domain of ZNF445 may be involved in this activation. Furthermore, we found that expression of ZNF445 can increase p42/44 MAPK, MEK and Raf-1 phosphorylation. These results clearly indicate that ZNF445 is a member of the zinc finger transcription factor family and may function in MAPK pathway through Raf-1/MEK/p42/44 MAPK signals.
Luo
Kuntian
K
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, 200433, P. R. China.
Yuan
Jian
J
Shan
Yuxi
Y
Li
Jie
J
Xu
Meng
M
Cui
Yanhui
Y
Tang
Wenwen
W
Wan
Bo
B
Zhang
Nailing
N
Wu
Yimin
Y
Yu
Long
L
D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3; D016384:Consensus Sequence; D017124:Conserved Sequence; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000502:physiology*; D005091:Exons; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D008970:Molecular Weight; D016366:Open Reading Frames; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D018808:Transcription Factor AP-1 / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D016335:Zinc Fingers / Q000502:physiology*
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; C502774:SRE protein, human; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D008156:Luciferases; D020928:Mitogen-Activated Protein Kinases