C. elegans ced-13 can promote apoptosis and is induced in response to DNA damage.
The p53 tumor suppressor promotes apoptosis in response to DNA damage. Here we describe the Caenorhabditis elegans gene ced-13, which encodes a conserved BH3-only protein. We show that ced-13 mRNA accumulates following DNA damage, and that this accumulation is dependent on an intact C. elegans cep-1/p53 gene. We demonstrate that CED-13 protein physically interacts with the antiapoptotic Bcl-2-related protein CED-9. Furthermore, overexpression of ced-13 in somatic cells leads to the death of cells that normally survive, and this death requires the core apoptotic pathway of C. elegans. Recent studies have implicated two BH3-only proteins, Noxa and PUMA, in p53-induced apoptosis in mammals. Our studies suggest that in addition to the BH3-only protein EGL-1, CED-13 might also promote apoptosis in the C. elegans germ line in response to p53 activation. We propose that an evolutionarily conserved pathway exists in which p53 promotes cell death by inducing expression of two BH3-only genes.
Schumacher
B
B
Max-Planck-Institute of Biochemistry, Am Klopferspitz 18A, 82152 Martinsried, Germany.
Schertel
C
C
Wittenburg
N
N
Tuck
S
S
Mitani
S
S
Gartner
A
A
Conradt
B
B
Shaham
S
S
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D002107:Caenorhabditis / Q000235:genetics; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004247:DNA / Q000235:genetics / Q000528:radiation effects; D004249:DNA Damage; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental / Q000528:radiation effects; D006360:Heat-Shock Proteins / Q000235:genetics; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D012097:Repressor Proteins / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology; D014965:X-Rays
D051017:Apoptosis Regulatory Proteins; C438244:CEP-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; C504038:Ced-13 protein, C elegans; C087233:Ced-9 protein, C elegans; C112486:EGL-1 protein, C elegans; D006360:Heat-Shock Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53; D004247:DNA