ABC50 promotes translation initiation in mammalian cells

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dc.contributor.authorWang, X.
dc.contributor.authorPaytubi, S.
dc.contributor.authorLam, Y.
dc.contributor.authorIzquierdo, L.
dc.contributor.authorHunter, M.
dc.contributor.authorJan, E.
dc.contributor.authorHundal, H.
dc.contributor.authorProud, C.
dc.date.issued2009
dc.description.abstractABC50 is an ATP-binding cassette (ABC) protein, which, unlike most ABC proteins, does not possess membrane-spanning domains. ABC50 interacts with eukaryotic initiation factor 2 (eIF2), which plays a key role in translation initiation and its control. ABC50 binds to ribosomes, and this interaction requires both the N-terminal domain and at least one ABC domain. Knockdown of ABC50 by RNA interference impaired translation of both cap-dependent and -independent reporters, consistent with a positive role for ABC50 in the function of eIF2, which is required for both types of translation initiation. Mutation of the Walker box A or B motifs in both ABC regions of ABC50 yielded a mutant protein that exerted a dominant-interfering phenotype with respect to protein synthesis and translation initiation. Importantly, although dominant-interfering mutants of ABC50 impaired cap-dependent translation, translation driven by certain internal ribosome entry segments was not inhibited. ABC50 is located in the cytoplasm and nucleoplasm but not in the nucleolus. Thus, ABC50 is not likely to be directly involved in early ribosomal biogenesis, unlike some other ABC proteins. Taken together, the present data show that ABC50 plays a key role in translation initiation and has functions that are distinct from those of other non-membrane ABC proteins.
dc.description.statementofresponsibilitySonia Paytubi, Xuemin Wang, Yun W. Lam, Luis Izquierdo, Mairi J. Hunter, Eric Jan, Harinder S. Hundal, and Christopher G. Proud
dc.identifier.citationJournal of Biological Chemistry, 2009; 284(36):24061-24073
dc.identifier.doi10.1074/jbc.M109.031625
dc.identifier.issn0021-9258
dc.identifier.issn1083-351X
dc.identifier.orcidProud, C. [0000-0003-0704-6442]
dc.identifier.urihttp://hdl.handle.net/2440/82607
dc.language.isoen
dc.publisherAmer Soc Biochemistry Molecular Biology Inc
dc.rights© 2009 by The American Society for Biochemistry and Molecular Biology, Inc
dc.source.urihttps://doi.org/10.1074/jbc.m109.031625
dc.subjectCell Line
dc.subjectRibosomes
dc.subjectHumans
dc.subjectATP-Binding Cassette Transporters
dc.subjectEukaryotic Initiation Factor-2
dc.subjectRNA Caps
dc.subjectRNA Interference
dc.subjectAmino Acid Motifs
dc.subjectProtein Structure, Tertiary
dc.subjectPeptide Chain Initiation, Translational
dc.subjectMutation
dc.titleABC50 promotes translation initiation in mammalian cells
dc.typeJournal article
pubs.publication-statusPublished

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