title: Differential expression of classical nuclear transport factors during cellular proliferation and differentiation.
abstract: We recently cloned six human importin a proteins that transport specific substrates in complex with importin beta into the nucleus. We now compared their absolute expression levels in different human cell lines. We examined their expression regulation during human cell proliferation and differentiation by means of specific antibodies. Proliferation inhibition by starvation of HeLa and HaCaT cells led to a marked decrease in the expression of various nuclear transport factors. In contrast, re-addition of serum increased alpha-importin expression. We analyzed two models for cell differentiation and found differential importin regulation. Stimulation of rat pancreatic AR42J cell differentiation towards a neuroendocrine phenotype with activin A or towards an acinar phenotype with dexamethasone, caused strong upregulation of importin alpha3 and alpha4 expression. Phorbol ester-induced differentiation of human leukemia (HL60) cells towards a macrophage phenotype led to downregulation of importin alpha1 and alpha4 expression after 72 hours. Similarly, importins alpha1 and alpha4 displayed a strong downregulation when HL60 cells were directed towards a neutrophil phenotype by DMSO treatment. This study is the first to assess all the human importin alpha isoforms in documenting differential nuclear transport factor regulation during cell proliferation and differentiation.
authors.affiliation: HELIOS Clinic / Franz Volhard Clinic at the Max Delbrueck Center, Medical Faculty of the Charité, Berlin, Germany. Koehler@fvk.charite-buch.de
authors.forename: Matthias
authors.initials: M
authors.lastname: Köhler
authors.forename: Anette
authors.initials: A
authors.lastname: Fiebeler
authors.forename: Maite
authors.initials: M
authors.lastname: Hartwig
authors.forename: Sebastian
authors.initials: S
authors.lastname: Thiel
authors.forename: Siegfried
authors.initials: S
authors.lastname: Prehn
authors.forename: Ralph
authors.initials: R
authors.lastname: Kettritz
authors.forename: Friedrich C
authors.initials: FC
authors.lastname: Luft
authors.forename: Enno
authors.initials: E
authors.lastname: Hartmann
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000502:physiology*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D015536:Down-Regulation; D006801:Humans; D028884:Karyopherins / Q000096:biosynthesis* / Q000378:metabolism; D010703:Phorbol Esters / Q000494:pharmacology; D020033:Protein Isoforms / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D014018:Tissue Distribution; D015854:Up-Regulation
chemical_list: D028884:Karyopherins; D010703:Phorbol Esters; D020033:Protein Isoforms; D011994:Recombinant Proteins; D003907:Dexamethasone