RRC ID 28649
Author Kominami K, Takagi C, Kurata T, Kitayama A, Nozaki M, Sawasaki T, Kuida K, Endo Y, Manabe N, Ueno N, Sakamaki K.
Title The initiator caspase, caspase-10beta, and the BH-3-only molecule, Bid, demonstrate evolutionary conservation in Xenopus of their pro-apoptotic activities in the extrinsic and intrinsic pathways.
Journal Genes Cells
Abstract Two major apoptotic signaling pathways have been defined in mammals, the extrinsic pathway, initiated by ligation of death receptors, and the intrinsic pathway, triggered by cytochrome c release from mitochondria. Here, we identified and characterized the Xenopus homologs of caspase-10 (xCaspase-10beta), a novel initiator caspase, and Bid (xBid), a BH3-only molecule of the Bcl-2 family involved in both the extrinsic and intrinsic pathways. Exogenous expression of these molecules induced apoptosis of mammalian cells. By biochemical and cytological analyses, we clarified that xCaspase-10beta and xBid exhibit structural and functional similarities to their mammalian orthologues. We also detected xCaspase-10beta and xBid transcripts during embryogenesis by whole-mount in situ hybridization and RT-PCR analysis. Microinjection of mRNA encoding a protease-defect xCaspase-10beta mutant into embryos resulted in irregular development. Enforced expression of active xBid induced cell death in developing embryos. Using transgenic frogs established to allow monitoring of caspase activation in vivo, we confirmed that this form of cell death is caspase-dependent apoptosis. Thus, we demonstrated that the machinery governing the extrinsic and intrinsic apoptotic pathways are already established in Xenopus embryos. Additionally, we propose that the functions of the initiator caspase and BH3-only molecule are evolutionarily conserved in vertebrates, functioning during embryonic development.
Volume 11(7)
Pages 701-17
Published 2006-7
DOI 10.1111/j.1365-2443.2006.00983.x
PMID 16824191
MeSH Amino Acid Sequence Animals Apoptosis Regulatory Proteins / genetics Apoptosis Regulatory Proteins / metabolism* BH3 Interacting Domain Death Agonist Protein / biosynthesis BH3 Interacting Domain Death Agonist Protein / genetics BH3 Interacting Domain Death Agonist Protein / metabolism* Caspase 10 Caspases / biosynthesis Caspases / genetics Caspases / metabolism* Chickens Evolution, Molecular Green Fluorescent Proteins / genetics Green Fluorescent Proteins / metabolism HeLa Cells Humans Mice Mitochondria / metabolism Molecular Sequence Data Peptide Hydrolases / metabolism RNA, Messenger / biosynthesis RNA, Messenger / genetics Sequence Alignment Transfection Xenopus / embryology Xenopus / genetics* Xenopus / metabolism
IF 2.048
Times Cited 10
DNA material PBX0108H11 (Xenopus Bid) (RDB08075)