Sequence specificity and transcriptional activation in the binding of lactoferrin to DNA

LACTOFERRIN, an iron-binding glycoprotein found in high concentrations in human milk and other epithelial secretions1 and in the secondary (specific) granules of neutrophils2, is thought to be responsible for primary defence against microbial infection, mainly as a result of lactoferrin sequestration of iron required for microbial growth3. Many other functions have been attributed to lactoferrin, including immunomodulation and cell growth regulation (reviewed in ref. 4). Some of these functions appear to be at least in part independent of the iron-binding activity of lactoferrin. It also has been consistently observed that lactoferrin interacts avidly with nucleic acids5–7. Lactoferrin enhancement of the activity of natural killer and lymphokine-activated killer cells in vitro is inhibited by RNA and DNA8. Lactoferrin taken up by K562 human myelogenous leukaemia cells appears in the nucleus where it is bound to DNA9. We report here that binding of lactoferrin to DNA occurs under stringent conditions with distinct sequence specificity, and that interaction between lactoferrin and these sequences intracellularly leads to transcriptional activation.

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