Delta-lactoferrin, an intracellular lactoferrin isoform that acts as a transcription factor.
Delta-lactoferrin (ΔLf) 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. ΔLf 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 ΔLf, its nucleocytoplasmic counterpart. ΔLf possesses antiproliferative properties and induces cell cycle arrest. It is an efficient transcription factor interacting in vivo via a ΔLf response element found in the Skp1, Bax, DcpS, and SelH promoters. Since ΔLf possesses different target genes, modifications in its activity or concentration may have crucial effects on cell homeostasis. Posttranslational modifications modulate ΔLf transcription factor activity. Our earlier investigations showed that O-GlcNAcylation negatively regulates ΔLf transcriptional activity, whilst inhibiting its ubiquitination and increasing its half-life. On the other hand, phosphorylation potentiates ΔLf transcriptional activity. Recently, we showed that ΔLf 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 ΔLf transcriptional activity depending on the type of target gene and cellular homeostasis.
Unité de Glycobiologie Structurale et Fonctionnelle, UMR 8576 CNRS-Université des Sciences et Technologies de Lille, IFR 148, 59655 Villeneuve d'Ascq, France. christophe.mariller@univ-lille1.fr
Christophe
C
Mariller
Stephan
S
Hardivillé
Esthelle
E
Hoedt
Isabelle
I
Huvent
Socorro
S
Pina-Canseco
Annick
A
Pierce
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016384:Consensus Sequence; D005786:Gene Expression Regulation; D006801:Humans; D007781:Lactoferrin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013499:Surface Properties; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D020033:Protein Isoforms; D014157:Transcription Factors; D007781:Lactoferrin