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Tandem CCCH Zinc Finger Proteins in mRNA Binding

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Zinc Finger Proteins

Part of the book series: Molecular Biology Intelligence Unit ((MBIU))

Summary

A small family of mammalian zinc finger proteins containing an unusual putative tandem zinc finger motif was identified approximately 13 years ago. The tandem zinc finger domain was characterized by two hypothetical fingers with identical Cx8Cx5Cx3H spacing, with exactly 18 amino acids between the carboxyl terminal H of the first zinc finger and the amino terminal C of the second zinc finger. The two fingers also shared a characteristic amino-terminal lead-in sequence of RYKTEL or a close variant. Although first thought to be transcription factors, these proteins are becoming better understood as the result of experiments with knockout mice for tristetraprolin (TTP), currently the best-studied member of the family. These mice developed a systemic inflammatory syndrome found to be secondary to elevations of tumor necrosis factor alpha (TNF) and possibly granulocyte-macrophage colony-stimulating factor (GM-CSF). These elevations were found to be due to stabilized mRNAs for these cytokines, and subsequent work found that TTP could bind to the AU-rich elements within the 3′-untranslated region of these mRNAs and destabilize them, apparently by initiating a process of 3′–5′ deadenylation. This chapter will summarize some of our current thinking about this small but interesting protein family, including binding site and binding domain characterization, and recent developments in mutagenesis and structure determination.

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Author information

Authors and Affiliations

  1. Office of Clinical Research and the Laboratory of Signal Transduction National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA

    Perry J. Blackshear, Ruth S. Phillips & Wi S. Lai

  2. Departments of Medicine and Biochemistry, Duke University Medical Center, Durham, North Carolina, USA

    Perry J. Blackshear

Authors
  1. Perry J. Blackshear
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  2. Ruth S. Phillips
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  3. Wi S. Lai
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Editor information

Editors and Affiliations

  1. Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA

    Shiro Iuchi

  2. Biological Engineering Division, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA

    Natalie Kuldell

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© 2005 Landes Bioscience/Eurekah.com and Kluwer Academic/Plenum Publishers

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Blackshear, P.J., Phillips, R.S., Lai, W.S. (2005). Tandem CCCH Zinc Finger Proteins in mRNA Binding. In: Iuchi, S., Kuldell, N. (eds) Zinc Finger Proteins. Molecular Biology Intelligence Unit. Springer, Boston, MA. https://doi.org/10.1007/0-387-27421-9_13

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