ABC50 promotes translation initiation in mammalian cells.
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.
Paytubi
Sonia
S
Division of Molecular Physiology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, United Kingdom.
Wang
Xuemin
X
Lam
Yun W
YW
Izquierdo
Luis
L
Hunter
Mairi J
MJ
Jan
Eric
E
Hundal
Harinder S
HS
Proud
Christopher G
CG
D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D020816:Amino Acid Motifs / Q000502:physiology; D002460:Cell Line; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009154:Mutation; D010442:Peptide Chain Initiation, Translational / Q000502:physiology*; D017434:Protein Structure, Tertiary / Q000502:physiology; D012315:RNA Caps / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism
C115776:ABCF1 protein, human; D018528:ATP-Binding Cassette Transporters; D015852:Eukaryotic Initiation Factor-2; D012315:RNA Caps