The transformation suppressor protein Pdcd4 shuttles between nucleus and cytoplasm and binds RNA.
The Pdcd4 gene has originally been isolated in a search for genes that are activated in cells undergoing apoptosis. Independent of these studies, the Pdcd4 gene has been implicated in the suppression of tumor-promoter-mediated transformation of keratinocytes and as a downstream target of Myb in hematopoietic cells. The Pdcd4 protein has weak homology to the eucaryotic translation initiation factor eIF4G and has been shown to interact with certain translation initiation factors. To explore the molecular function of the Pdcd4 protein, we have studied its subcellular localization. We show that the Pdcd4 protein is a predominantly nuclear protein under normal growth conditions and that it is exported from the nucleus by a leptomycin B-sensitive mechanism upon serum withdrawal. The protein contains two nuclear export signals, one of which is very potent. In addition, we demonstrate that the Pdcd4 protein has RNA-binding activity and that the sequences involved in RNA-binding are located in the amino-terminal part of the protein. Taken together, our data raise the possibility that Pdcd4 is involved in some aspect of nuclear RNA metabolism in addition to its suspected role in protein translation.
Böhm
Maret
M
Institut für Biochemie, Westfälische-Wilhelms-Universität Münster, Wilhelm-Klemm-Str. 2, D-48149 Münster1, Germany.
Sawicka
Kirsty
K
Siebrasse
Jan Peter
JP
Brehmer-Fastnacht
Anne
A
Peters
Reiner
R
Klempnauer
Karl-Heinz
KH
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D001665:Binding Sites; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured / Q000378:metabolism; D002645:Chickens; D002999:Clone Cells / Q000378:metabolism; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D051379:Mice; D008845:Microinjections; D008969:Molecular Sequence Data; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D021381:Protein Transport / Q000187:drug effects; D012313:RNA / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D014162:Transfection
D051017:Apoptosis Regulatory Proteins; D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors; D005231:Fatty Acids, Unsaturated; C498443:Pdcd4 protein, mouse; D016601:RNA-Binding Proteins; D012313:RNA; D011493:Protein Kinase C; C038753:leptomycin B