Role of the Sec61 translocon in EGF receptor trafficking to the nucleus and gene expression.
The epidermal growth factor (EGF)-dependent trafficking of the intact EGF receptor to the nucleus and its requirement for growth factor induction of cyclin D and other genes has been reported. Unresolved is the mechanism by which this or other transmembrane proteins are excised from a lipid bilayer before nuclear translocalization. We report that, after the addition of EGF, the cell surface EGF receptor is trafficked to the endoplasmic reticulum (ER) where it associates with Sec61beta, a component of the Sec61 translocon, and is retrotranslocated from the ER to the cytoplasm. Abrogation of Sec61beta expression prevents EGF-dependent localization of EGF receptors to the nucleus and expression of cyclin D. This indicates that EGF receptors are trafficked from the ER to the nucleus by a novel pathway that involves the Sec61 translocon.
Liao
Hong-Jun
HJ
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232-0146, USA.
Carpenter
Graham
G
D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D056741:Cyclin D; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D011485:Protein Binding / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000069816:SEC Translocation Channels
D056741:Cyclin D; D016213:Cyclins; D008565:Membrane Proteins; D012333:RNA, Messenger; D000069816:SEC Translocation Channels; C499388:SEC61B protein, human; D004815:Epidermal Growth Factor; D066246:ErbB Receptors