Delta-lactoferrin, an intracellular lactoferrin isoform that acts as a transcription factor.
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Mariller C, Hardiville S, Hoedt E, Huvent I, Pina-Canseco S, Pierce A
Delta-lactoferrin, an intracellular lactoferrin isoform that acts as a transcription factor.
Biochem Cell Biol. 2012 Jun;90(3):307-19. doi: 10.1139/o11-070. Epub 2012 Feb 9.
- PubMed ID
- 22320386 [ View in PubMed]
- Abstract
Delta-lactoferrin (DeltaLf) 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. DeltaLf 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 DeltaLf, its nucleocytoplasmic counterpart. DeltaLf possesses antiproliferative properties and induces cell cycle arrest. It is an efficient transcription factor interacting in vivo via a DeltaLf response element found in the Skp1, Bax, DcpS, and SelH promoters. Since DeltaLf possesses different target genes, modifications in its activity or concentration may have crucial effects on cell homeostasis. Posttranslational modifications modulate DeltaLf transcription factor activity. Our earlier investigations showed that O-GlcNAcylation negatively regulates DeltaLf transcriptional activity, whilst inhibiting its ubiquitination and increasing its half-life. On the other hand, phosphorylation potentiates DeltaLf transcriptional activity. Recently, we showed that DeltaLf 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 DeltaLf transcriptional activity depending on the type of target gene and cellular homeostasis.