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Publications (2)5.35 Total impact

  • Article: WDR26: a novel Gbeta-like protein, suppresses MAPK signaling pathway.
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    ABSTRACT: WD40 repeat proteins play important roles in a variety of cellular functions, including cell growth, proliferation, apoptosis, and intracellular signal transduction. Mitogen-activated protein kinases (MAPKs) are evolutionary conserved enzymes in cell signal transduction connecting cell-surface receptors to critical regulatory targets within cells and control cell survival, adaptation, and proliferation. Previous studies revealed that G-protein coupled receptors (GPCRs) play important roles in the signal transduction from extracellular stimuli to MAPKs and the WD40-containing Gbeta proteins as well as Gbeta-like proteins are involved in the stimulation and regulation of the MAPK signaling pathways. Here we report the identification and characterization of a novel human WD40 repeat protein, WD40 repeat protein 26 (WDR26). The cDNA of WDR26 is 3,729 bp, encoding a Gbeta-like protein of 514 amino acids in the cytoplasm. The protein is highly conserved in evolution across different species from yeast, Drosophila, mouse, to human. Northern blot analysis indicates that WDR26 is expressed in most of the examined human tissues, especially at a high level in skeletal muscle. Overexpression of WDR26 in the cell inhibits the transcriptional activities of ETS proteins, ELK-1 and c-fos serum response element (SRE), mediated by MEKK1. These results suggest that WDR26 may act as a negative regulator in MAPK signaling pathway and play an important role in cell signal transduction.
    Journal of Cellular Biochemistry 11/2004; 93(3):579-87. · 2.87 Impact Factor
  • Article: ZNF411, a novel KRAB-containing zinc-finger protein, suppresses MAP kinase signaling pathway.
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    ABSTRACT: Cardiac differentiation involves a cascade of coordinated gene expression that regulates cell proliferation and matrix protein formation in a defined temporo-spatial manner. The zinc-finger-containing transcription factor has been implicated as a critical regulator of multiple cardiac-expressed genes as well as a regulator of inducible gene expression in response to hypertrophic stimulation. Mitogen-activated protein kinase (MAPK) signal transduction pathways are among the most widespread mechanisms of eukaryotic cell regulation. The MAPKs function inside the nucleus and target transcription factors that are prebound to DNA. Many transcription factors are probably important MAPK targets. Here, we have cloned a new zinc-finger gene named ZNF411 using degenerate primers from an early embryo heart cDNA library, which mapped to 19p13.11. The ZNF411 gene consists of 2360 nucleotides and encodes a protein of 499 amino acids with an amino-terminal KRAB domain and eleven carboxy-terminal C2H2 zinc-finger units. Northern blot analysis indicates that a 2.4 kb transcript specific for ZNF411 is expressed in heart, skeletal muscle, and placenta at adult stage and is expressed in most of the examined embryonic tissues, especially at a higher level in skeletal muscle, heart, and pancreas. ZNF411 protein distributes evenly in nuclei when overexpressed in the cells. Reporter gene assays show that ZNF411 is a transcriptional repressor and overexpression of ZNF411 in the COS-7 cells inhibits the transcriptional activities of AP-1 and SRE. These results indicate that ZNF411 is a member of the zinc-finger transcription factor family and may be involved in the heart development, and it probably works as a negative regulator in MAPK signaling pathway.
    Biochemical and Biophysical Research Communications 08/2004; 320(1):45-53. · 2.48 Impact Factor