|Human, Mouse, Rat|
Application Methods: Western Blotting
Background: Eukaryotic initiation factor 5A (eIF5A) is an mRNA-binding protein that is involved in translation elongation and plays an important role in promoting translation of polyproline motifs (1-4). The eIF5A (eIF5A1) and eIF5A2 genes encode the two vertebrate eIF5A isoforms. While eIF5A1 is expressed constitutively in all tissues, eIF5A2 is mainly expressed in gonads. eIF5A and eIF5A2 are the only identified proteins that contain the distinctive amino acid hypusine, which is generated posttranslationally from lysine through a highly conserved polyamine metabolism pathway. eIF5A function and hypusine modification are both essential for cell proliferation, as knock down of eIF5A expression or blocking eIF5A hypusine modification suppresses cancer cell proliferation (5-7). Interestingly, eIF5A is an identified component of a tumor suppressor network of the polyamine-hypusine axis. Co-suppression of both eIF5A and adenosylmethionine decarboxylase 1 (AMD1) promotes lymphomagenesis in mice, while heterozygous deletions of the corresponding AMD1 and eIF5A genes often occur together in human lymphomas (8).
|Human, Monkey, Mouse|
Application Methods: Immunofluorescence (Immunocytochemistry), Immunohistochemistry (Paraffin), Immunoprecipitation, Western Blotting
Background: Exportins are a family of seven proteins that are responsible for intracellular transport. Exportin-1, also known as chromosome region maintenance 1 (CRM1), is a protein essential for nuclear export of hundreds of proteins, mRNAs, and rRNAs (1-3). Exportin-1 binds to substrates with nuclear export signals (NESs) rich in leucine and other hydrophobic amino acids (4). These hydrophobic sequences form an alpha-helix-loop that can bind to the exportin-1 hydrophobic groove (5). Studies have shown that these NESs can be modified either by protein modifications or by mutation to regulate exportin-1 binding (6-7). Targets of exportin-1 include many tumor suppressors, such as Rb, p53, FoxO1, BAF47, as well as oncoproteins, such as p21 and p27 (1). In addition, Myc can upregulate exportin-1 during biogenesis, where it can export newly formed 40S and 60S subunits from the nucleoli (8-9).Inhibition of nuclear export has been pursued for therapeutic application since the finding that leptomycin B could suppress HIV replication by suppressing the ability of exportin-1 to export the HIV-1 protein Rev (2, 10). Overexpression of exportin-1 has been associated with poor prognosis in various cancer types (11-13). Genomic approaches and development of inhibitors have identified exportin-1 as a druggable target (14-16). The use of various inhibitors of exportin-1 is also being explored in various antiviral therapies (17-18).