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

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 IMP?-binding-like (IBBL) domain within Ei24. We show that Ei24 can bind specifically to IMP?1 and IMP?2, but not other IMPs, and use a mutated IMP?1 derivative to show that Ei24 binds to the same site on IMP?1 as the IMP? IBB. Ectopic expression of Ei24 reduced the extent of IMP?1- or IMP?/?1-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 IMP?1 and IMP?2 to impede their normal role in nuclear import, shedding new light on the cellular functions of Ei24 and its tumor suppressor role.

SUBMITTER: Lieu KG 

PROVIDER: S-EPMC4018778 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature