title: The cell death machinery controlled by Bax and Bcl-XL is evolutionarily conserved in Ciona intestinalis.
abstract: Bax and Bcl-XL are key regulators of apoptosis in mammals. Here we report the functional characterization of two Bcl-2 homologues, ciBax and ciBcl-XL, in a basal invertebrate-chordate ascidian Ciona intestinalis. CiBax is a Ciona homologue of the BH1-3 pro-apoptotic protein Bax, whereas ciBcl-XL is a Bcl-XL-like anti-apoptotic protein. Molecular modeling analysis showed that ciBax and ciBcl-XL share both sequence and structural similarities to human Bax and Bcl-XL, respectively. Like their human counterparts, ciBax could form a homodimer or oligomers as well as heterodimerize with ciBcl-XL, and overexpression of ciBax caused apoptosis that could be attenuated by ciBcl-XL. Mutagenesis studies showed that the BH3 domain of ciBax is critical for its cell death-inducing function and also for its interaction with ciBcl-XL. In Ciona embryos, ectopic expression of ciBax but not its BH3 deletion mutant resulted in cell dissociation and apoptosis after late gastrula stage of embryonic development. Moreover, not only wild type ciBcl-XL but also a mutant ciBcl-XL(F101V), which is unable to interact with ciBax, could block cell dissociation and developmental deficit in Ciona embryos induced by overexpression of ciBax. Taken together, these findings suggest that functional homologues of both the BH1-3 death effector Bax and the pro-survival Bcl-XL exist in sea squirt Ciona intestinalis, and they control the cell death machinery independent of their heterodimerization.
authors.affiliation: Department of Interdisciplinary Oncology, Drug Discovery Program, H. Lee Moffitt Cancer Center & Research Institute, University of South Florida College of Medicine, 12902 Magnolia Drive, Tampa, FL 33612, USA.
authors.forename: N
authors.initials: N
authors.lastname: Takada
authors.forename: H
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: K
authors.initials: K
authors.lastname: Shida
authors.forename: D
authors.initials: D
authors.lastname: Terajima
authors.forename: Y
authors.initials: Y
authors.lastname: Satou
authors.forename: A
authors.initials: A
authors.lastname: Kasuya
authors.forename: N
authors.initials: N
authors.lastname: Satoh
authors.forename: M
authors.initials: M
authors.lastname: Satake
authors.forename: H-G
authors.initials: HG
authors.lastname: Wang
mesh_terms: D000818:Animals; D005075:Biological Evolution; D016923:Cell Death; D002938:Ciona intestinalis / Q000166:cytology* / Q000196:embryology; D019281:Dimerization; D004625:Embryo, Nonmammalian / Q000002:abnormalities / Q000166:cytology; D006367:HeLa Cells; D006801:Humans; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D051028:bcl-2-Associated X Protein / Q000737:chemistry / Q000378:metabolism*; D051020:bcl-X Protein / Q000737:chemistry / Q000378:metabolism*
chemical_list: D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein