Pax2/5/8 proteins promote cell survival in C. elegans.
Programmed cell death, or apoptosis, plays an important role during normal development, and is disrupted in a range of disease states. Although the key molecular events that occur during apoptosis are well characterized, less is known about the regulatory inputs that influence whether a cell will live or die. Work in mouse and human cells has shown that Pax transcription factors can influence cell death and promote cell survival, but the mechanism for their activity is not clear. Here, we show that two Pax2/5/8-related genes (egl-38 and pax-2) influence both somatic and germline cell death in C. elegans. Using genetic and molecular experiments, we show that the Pax proteins act as transcriptional regulators of ced-9, the C. elegans bcl-2 gene. These results identify a mechanism for Pax2/5/8-mediated regulation of cell death, and underscore the importance of transcriptional regulation of core apoptotic pathway genes in influencing cell survival.
Park
DonHa
D
Department of Molecular Genetics, Ohio State University, Columbus, OH 43210 USA.
Jia
Hongtao
H
Rajakumar
Vandana
V
Chamberlin
Helen M
HM
D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000033:anatomy & histology / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D005854:Germ Cells / Q000166:cytology / Q000502:physiology; D006801:Humans; D051379:Mice; D009030:Mosaicism; D009876:Operon; D051762:PAX2 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D051757:PAX5 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D034622:RNA Interference; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D051017:Apoptosis Regulatory Proteins; D029742:Caenorhabditis elegans Proteins; C087233:Ced-9 protein, C elegans; D004268:DNA-Binding Proteins; D051762:PAX2 Transcription Factor; D051757:PAX5 Transcription Factor; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014157:Transcription Factors; C497470:egl-38 protein, C elegans