The Midblastula Transition in Xenopus Embryos Activates Multiple Pathways to Prevent Apoptosis in Response to DNA Damage

• Published in: Proceedings of the National Academy of Sciences - PNAS 2001-01, Vol.98 (3), p.1006-1011
• Main Authors: Finkielstein, Carla V., Lewellyn, Andrea L., Maller, James L.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Apoptosis; Apoptosis - physiology; bax protein; Bcl-2 protein; Biological Sciences; Blastocyst - cytology; Blastocyst - physiology; Blastocyst - radiation effects; CDC2-CDC28 Kinases; Cdk2 protein; Cdk4 protein; Cell cycle; Cell Cycle - physiology; Cell Cycle - radiation effects; Cell Cycle Proteins; Cellular biology; cyclin A; Cyclin D; Cyclin-Dependent Kinase 2; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase Inhibitor p27; Cyclin-Dependent Kinases - antagonists & inhibitors; Cyclin-Dependent Kinases - metabolism; Cyclins; Cyclins - metabolism; Deoxyribonucleic acid; DNA; DNA Damage; Embryo, Nonmammalian - cytology; Embryo, Nonmammalian - physiology; Embryos; Freshwater; G1 Phase; Ionizing radiation; Irradiation; Messenger RNA; Microtubule-Associated Proteins - metabolism; Models, Biological; Molecular Sequence Data; Morphogenesis; Phosphorylation; Protein-Serine-Threonine Kinases - metabolism; Proteins; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-bcl-2 - metabolism; S Phase; Tumor Suppressor Proteins; Xenopus; Xenopus - embryology; Xenopus Proteins; Xic1 protein
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.98.3.1006

Apoptosis is controlled by a complex interplay between regulatory proteins. Previous work has shown that Xenopus embryos remove damaged cells by apoptosis when irradiated before, but not after, the midblastula transition (MBT). Here we demonstrate that Akt/protein kinase B is activated and mediates an antiapoptotic signal only in embryos irradiated after the MBT. In addition, an increase in xBcl-2/xBax oligomerization and a decrease in xBax homodimerization promote a protective effect against apoptosis only after the MBT. The post-MBT survival mechanism arrests cells in G1phase by increasing expression of the cyclin-dependent kinase inhibitor p27Xic1. p27Xic1associates with cyclin D/Cdk4 and cyclin A/Cdk2 complexes to cause G1S arrest, perhaps allowing more time for DNA repair. Taken together, the results define the DNA damage response as an element of the MBT and indicate that multiple mechanisms prevent apoptosis after the MBT.