Delta-lactoferrin, an intracellular lactoferrin isoform that acts as a transcription factor

Delta-lactoferrin (Delta Lf) is a transcription factor of which the expression is downregulated in cancer. It is a healthy tissue marker and a high expression level of its transcripts was correlated with a good prognosis in breast cancer. Delta Lf results from alternative promoter usage of the hLf gene leading to the production of 2 isoforms with alternative N-termini: lactoferrin, which is secreted, and Delta Lf, its nucleocytoplasmic counterpart. Delta Lf possesses antiproliferative properties and induces cell cycle arrest. It is an efficient transcription factor interacting in vivo via a Delta Lf response element found in the Skp1, Bax, DcpS, and SelH promoters. Since Delta Lf possesses different target genes, modifications in its activity or concentration may have crucial effects on cell homeostasis. Posttranslational modifications modulate Delta Lf transcription factor activity. Our earlier investigations showed that O-GlcNAcylation negatively regulates Delta Lf transcriptional activity, whilst inhibiting its ubiquitination and increasing its half-life. On the other hand, phosphorylation potentiates Delta Lf transcriptional activity. Recently, we showed that Delta Lf is also modified by SUMOylation. Therefore, cooperation and (or) competition among SUMOylation, ubiquitination, phosphorylation, and O-GlcNAcylation may contribute to the establishment of a fine regulation of Delta Lf transcriptional activity depending on the type of target gene and cellular homeostasis.