title: Two new isoforms of the human hepatoma-derived growth factor interact with components of the cytoskeleton.
abstract: Hepatoma-derived growth factor (HDGF) is involved in diverse, apparently unrelated processes, such as cell proliferation, apoptosis, DNA-repair, transcriptional control, ribosome biogenesis and cell migration. Most of the interactions of HDGF with diverse molecules has been assigned to the hath region of HDGF. In this study we describe two previously unknown HDGF isoforms, HDGF-B and HDGF-C, generated via alternative splicing with structurally unrelated N-terminal regions of their hath region, which is clearly different from the well described isoform, HDGF-A. In silico modeling revealed striking differences near the PHWP motif, an essential part of the binding site for glycosaminoglycans and DNA/RNA. This observation prompted the hypothesis that these isoforms would have distinct interaction patterns with correspondingly diverse roles on cellular processes. Indeed, we discovered specific associations of HDGF-B and HDGF-C with cytoskeleton elements, such as tubulin and dynein, suggesting previously unknown functions of HDGF in retrograde transport, site directed localization and/or cytoskeleton organization. In contrast, the main isoform HDGF-A does not interact directly with the cytoskeleton, but via RNA with messenger ribonucleoprotein (mRNP) complexes. In summary, the discovery of HDGF splice variants with their discrete binding activities and subcellular distributions opened new avenues for understanding its biological function and importance.
authors: Jessica
authors: J
authors: Nüße
authors: Ursula
authors: U
authors: Mirastschijski
authors: Mario
authors: M
authors: Waespy
authors: Janina
authors: J
authors: Oetjen
authors: Nadine
authors: N
authors: Brandes
authors: Osmond
authors: O
authors: Rebello
authors: Federico
authors: F
authors: Paroni
authors: Sørge
authors: S
authors: Kelm
authors: Frank
authors: F
authors: Dietz
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D002522:Chlorocebus aethiops; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism*; D004398:Dyneins / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D061251:Primary Cell Culture; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014404:Tubulin / Q000378:metabolism
chemical_list: D003598:Cytoskeletal Proteins; D036341:Intercellular Signaling Peptides and Proteins; D020033:Protein Isoforms; D014404:Tubulin; C051610:hepatoma-derived growth factor; D004398:Dyneins