ABC50 promotes translation initiation in mammalian cells

Sonia Paytubi, Xuemin Wang, Yun W. Lam, Luis Izquierdo, Mairi J. Hunter, Eric Jan, Harinder S. Hundal, Christopher G. Proud

    Research output: Contribution to journalArticle

    54 Citations (Scopus)

    Abstract

    ABC50 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.

    Original languageEnglish
    Pages (from-to)24061-24073
    Number of pages13
    JournalJournal of Biological Chemistry
    Volume284
    Issue number36
    DOIs
    Publication statusPublished - 4 Sep 2009

    Keywords

    • BINDING CASSETTE PROTEIN
    • HEPATITIS-C VIRUS
    • ELONGATION FACTOR-III
    • ATP-DEPENDENT MANNER
    • RIBOSOME ENTRY SITE
    • KINASE GCN2
    • NUCLEAR-ENVELOPE
    • P-GLYCOPROTEIN
    • BIOGENESIS
    • COMPLEX

    Cite this

    Paytubi, S., Wang, X., Lam, Y. W., Izquierdo, L., Hunter, M. J., Jan, E., ... Proud, C. G. (2009). ABC50 promotes translation initiation in mammalian cells. Journal of Biological Chemistry, 284(36), 24061-24073. https://doi.org/10.1074/jbc.M109.031625
    Paytubi, Sonia ; Wang, Xuemin ; Lam, Yun W. ; Izquierdo, Luis ; Hunter, Mairi J. ; Jan, Eric ; Hundal, Harinder S. ; Proud, Christopher G. / ABC50 promotes translation initiation in mammalian cells. In: Journal of Biological Chemistry. 2009 ; Vol. 284, No. 36. pp. 24061-24073.
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    Paytubi, S, Wang, X, Lam, YW, Izquierdo, L, Hunter, MJ, Jan, E, Hundal, HS & Proud, CG 2009, 'ABC50 promotes translation initiation in mammalian cells', Journal of Biological Chemistry, vol. 284, no. 36, pp. 24061-24073. https://doi.org/10.1074/jbc.M109.031625

    ABC50 promotes translation initiation in mammalian cells. / Paytubi, Sonia; Wang, Xuemin; Lam, Yun W.; Izquierdo, Luis; Hunter, Mairi J.; Jan, Eric; Hundal, Harinder S.; Proud, Christopher G.

    In: Journal of Biological Chemistry, Vol. 284, No. 36, 04.09.2009, p. 24061-24073.

    Research output: Contribution to journalArticle

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    T1 - ABC50 promotes translation initiation in mammalian cells

    AU - Paytubi, Sonia

    AU - Wang, Xuemin

    AU - Lam, Yun W.

    AU - Izquierdo, Luis

    AU - Hunter, Mairi J.

    AU - Jan, Eric

    AU - Hundal, Harinder S.

    AU - Proud, Christopher G.

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    N2 - ABC50 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.

    AB - ABC50 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.

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    KW - RIBOSOME ENTRY SITE

    KW - KINASE GCN2

    KW - NUCLEAR-ENVELOPE

    KW - P-GLYCOPROTEIN

    KW - BIOGENESIS

    KW - COMPLEX

    U2 - 10.1074/jbc.M109.031625

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    JF - Journal of Biological Chemistry

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    ER -

    Paytubi S, Wang X, Lam YW, Izquierdo L, Hunter MJ, Jan E et al. ABC50 promotes translation initiation in mammalian cells. Journal of Biological Chemistry. 2009 Sep 4;284(36):24061-24073. https://doi.org/10.1074/jbc.M109.031625