Z-DNA-binding protein 1, also known as DNA-dependent activator of IFN-regulatory factors (DAI) and DLM-1, is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

that in humans is encoded by the ''ZBP1''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

. ZBP1 is also an abbreviation for chicken or rat β-actin zipcode-binding protein 1, a homolog of the human insulin-like growth factor 2 mRNA-binding protein 1 ( IMP-1) and murine

CRD-BP The mouse Coding Region Determinant-Binding Protein (CRD-BP) is an RNA-binding protein.Doyle, G., et al. 1998. The c-myc¬ coding region determinant-binding protein: a member of a family of KH domain RNA-binding proteins. Nuc. Acid. Res. 26:5036-504 ...

, the proteins involved in mRNA transport ( RNA-binding proteins, RBPs).

Function

DLM1 encodes a

Z-DNA Z-DNA is one of the many possible double helical structures of DNA. It is a left-handed double helical structure in which the helix winds to the left in a zigzag pattern, instead of to the right, like the more common B-DNA form. Z-DNA is thought ...

binding protein. Z-DNA formation is a dynamic process, largely controlled by the amount of

supercoiling DNA supercoiling refers to the amount of twist in a particular DNA strand, which determines the amount of strain on it. A given strand may be "positively supercoiled" or "negatively supercoiled" (more or less tightly wound). The amount of a st ...

. ZBP1 recognizes DNA in the cytoplasm as an antiviral mechanism. Viral life cycles often include steps where DNA is exposed in the cytoplasm. DNA is normally contained in the nucleus of a cell, and therefore cells use proteins like ZBP1 as an indicator of a viral infection. Once ZBP1 is activated, it increases the production of antiviral cytokines such as

interferon beta The type-I interferons (IFN) are cytokines which play essential roles in inflammation, immunoregulation, tumor cells recognition, and T-cell responses. In the human genome, a cluster of thirteen functional IFN genes is located at the 9p21.3 cyto ...

. DLM1 then binds to cytosolic Viral DNA using two Z-DNA-binding domains (Zα and Zβ) at its N-terminus along with a DNA binding domain (D3). The role of ZBP1 in DNA sensing has been questioned. It has been found to sense Influenza A Virus (IAV) infection and induce cell death. Since DNA is not synthesized in any stage of IAV life cycle, DNA sensing playing a role in this context is unlikely. However, recent investigation has found that ZBP1 is capable of sensing Z-form RNAs produced during IAV infection, cumulating in a form of caspase independent, inflammatory cell death called necroptosis. A follow up study identified that ZBP1 senses the IAV ribonucleoprotein complex to induce cell death. A more recent study has identified transcription factor IRF1 as the upstream regulator of ZBP1 expression. Zipcode binding protein 1 (ZBP1) was shown to regulate dendritogenesis (

dendrite Dendrites (from Greek δένδρον ''déndron'', "tree"), also dendrons, are branched protoplasmic extensions of a nerve cell that propagate the electrochemical stimulation received from other neural cells to the cell body, or soma, of the n ...

formation) in hippocampal neurons. This protein is different from the nucleic acid sensor ZBP1.

Function

References

Further reading