The Hsp90 inhibitor geldanamycin abrogates colocalization of eIF4E and eIF4E-transporter into stress granules and association of eIF4E with eIF4G.
The eukaryotic translation initiation factor eIF4E plays a critical role in the control of translation initiation through binding to the mRNA 5' cap structure. eIF4E is also a component of processing bodies and stress granules, which are two types of cytoplasmic RNA granule in which translationally inactivated mRNAs accumulate. We found that treatment with the Hsp90 inhibitor geldanamycin leads to a substantial reduction in the number of HeLa cells that contain processing bodies. In contrast, stress granules are not disrupted but seem to be only partially affected by the inhibition of Hsp90. However, it is striking that eIF4E as well as its binding partner eIF4E transporter (4E-T), which mediates the import of eIF4E into the nucleus, are obviously lost from stress granules. Furthermore, the amount of eIF4G that is associated with the cap via eIF4E is reduced by geldanamycin treatment. Thus, the chaperone activity of Hsp90 probably contributes to the correct localization of eIF4E and 4E-T to stress granules and also to the interaction between eIF4E and eIF4G, both of which may be needed for eIF4E to acquire the physiological functionality that underlies the mechanism of translation initiation.
Graduate School of Agricultural and Life Sciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
Yukari
Y
Suzuki
Michiko
M
Minami
Miho
M
Suzuki
Keiko
K
Abe
Shuhei
S
Zenno
Masafumi
M
Tsujimoto
Ken
K
Matsumoto
Yasufumi
Y
Minami
D016227:Benzoquinones / Q000494:pharmacology*; D003594:Cytoplasmic Granules / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism*; D039603:Eukaryotic Initiation Factor-4G / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D047029:Lactams, Macrocyclic / Q000494:pharmacology*; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism*; D010442:Peptide Chain Initiation, Translational / Q000187:drug effects / Q000502:physiology; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D012315:RNA Caps / Q000378:metabolism
D016227:Benzoquinones; C411571:EIF4ENIF1 protein, human; C113920:EIF4G1 protein, human; D004791:Enzyme Inhibitors; D039561:Eukaryotic Initiation Factor-4E; D039603:Eukaryotic Initiation Factor-4G; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D029543:Nucleocytoplasmic Transport Proteins; D012315:RNA Caps; C001277:geldanamycin