p27(BBP)/eIF6 acts as an anti-apoptotic factor upstream of Bcl-2 during Xenopus laevis development.
p27(BBP)/eIF6 (beta4-binding protein/eukaryotic initiation factor 6) regulates the joining of 40S and 60S ribosomal subunits, on receptor for activated C kinase 1 binding and protein kinase C phosphorylation in serine 235. In Xenopus, p27(BBP)/eIF6 is abundantly expressed in the majority of the embryonic anlagen. Although p27(BBP)/eIF6 abundance may be required for a general regulation of protein synthesis, our data suggest that p27(BBP)/eIF6 may target the translation of specific mRNAs. We injected Xp27(BBP)/eIF6 mRNA in one blastomere of two-cell-stage embryos and obtained a bent phenotype, the curvature being lateral with respect to the embryo antero-posterior axis. The injected side had fewer apoptotic cells than the uninjected side, whereas cell proliferation appeared unaffected. Accordingly, in Xp27(BBP)/eIF6 morphants, endogenous apoptosis increased. Injection of Xp27(BBP)/eIF6 point mutants indicated that the anti-apoptotic action of Xp27(BBP)/eIF6 requires the conserved S235. The bent phenotype was also obtained with B-cell lymphoma gene-2 (Bcl-2) overexpression and was rescued by Bcl-2-associated X protein (Bax)/Xp27(BBP)/eIF6 co-injection. In addition, embryos overexpressing Xp27(BBP)/eIF6 had a higher amount of Bcl-2 and an unchanged amount of Bax with respect to controls. In Xp27(BBP)/eIF6 morphants, Bcl-2 levels were unaffected and Bax levels were higher than in the controls. Thus, we propose that Xp27(BBP)/eIF6 is part of a mechanism acting on the specific translation of messengers regulating cell survival. In particular, we suggest that Xp27(BBP)/eIF6 may regulate the translation of factors upstream of Bcl-2/Bax.
Department of Structural and Functional Biology, University of Naples Federico II, Naples, Italy.
N
N
De Marco
L
L
Iannone
R
R
Carotenuto
S
S
Biffo
A
A
Vitale
C
C
Campanella
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D015536:Down-Regulation / Q000502:physiology; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000196:embryology / Q000502:physiology; D039642:Eukaryotic Initiation Factors; D005260:Female; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000235:genetics; D007381:Intermediate Filament Proteins / Q000235:genetics* / Q000378:metabolism; D016296:Mutagenesis / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012270:Ribosomes / Q000502:physiology; D029867:Xenopus Proteins / Q000235:genetics* / Q000378:metabolism; D014982:Xenopus laevis / Q000196:embryology / Q000235:genetics*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D002352:Carrier Proteins; D039642:Eukaryotic Initiation Factors; D007381:Intermediate Filament Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D029867:Xenopus Proteins; D051028:bcl-2-Associated X Protein; C504182:eIF6 protein, Xenopus; D049452:Green Fluorescent Proteins