The p53-induced factor Ei24 inhibits nuclear import through an importin beta-binding-like domain

Kim G Lieu, Eun-Hee Shim, Jinling Wang, Ravi K Lokareddy, Tao Tao, Gino Cingolani, Gerard P Zambetti, David A Jans

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19 Citations (Scopus)

Abstract

The etoposide-induced protein Ei24 was initially identified as a p53-responsive, proapoptotic factor, but no clear function has been described. Here, we use a nonbiased proteomics approach to identify members of the importin (IMP) family of nuclear transporters as interactors of Ei24 and characterize an IMPbeta-binding-like (IBBL) domain within Ei24. We show that Ei24 can bind specifically to IMPbeta1 and IMPalpha2, but not other IMPs, and use a mutated IMPbeta1 derivative to show that Ei24 binds to the same site on IMPbeta1 as the IMPalpha IBB. Ectopic expression of Ei24 reduced the extent of IMPbeta1- or IMPalpha/beta1-dependent nuclear protein import specifically, whereas specific alanine substitutions within the IBBL abrogated this activity. Induction of endogenous Ei24 expression through etoposide treatment similarly inhibited nuclear import in a mouse embryonic fibroblast model. Thus, Ei24 can bind specifically to IMPbeta1 and IMPalpha2 to impede their normal role in nuclear import, shedding new light on the cellular functions of Ei24 and its tumor suppressor role.
Original languageEnglish
Pages (from-to)301 - 312
Number of pages12
JournalJournal of Cell Biology
Volume205
Issue number3
DOIs
Publication statusPublished - 2014

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