A Proline- and Glutamine-Rich Protein Promotes Apoptosis in Neuronal Cells
| Autor: | Toru Miki, Marsha Rich Rosner, Ignatius Gomes, Wen Xiong |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Programmed cell death
DNA Complementary Proline Glutamine Cellular differentiation Molecular Sequence Data Codon Initiator Apoptosis Nerve Tissue Proteins Hippocampal formation Biology Fibroblast growth factor Biochemistry Cellular and Molecular Neuroscience In Situ Nick-End Labeling Animals RNA Messenger fas Receptor Cloning Molecular Genes Immediate-Early Phorbol 12 13-Dibutyrate Cell Line Transformed Neurons Base Sequence Sequence Homology Amino Acid Cell Differentiation Sequence Analysis DNA Blotting Northern Fas receptor Molecular biology Rats Fibroblast Growth Factors Cell culture Protein Biosynthesis Carcinogens Septal Nuclei Rabbits Apoptosis Regulatory Proteins Immediate early gene Transcription Factors |
| Zdroj: | Journal of Neurochemistry. 73:612-622 |
| ISSN: | 0022-3042 |
| Popis: | During development, excess neurons are eliminated by programmed cell death. Similarly, conditionally immortalized (SV40-Tts) rat hippocampal and septal cells undergo cell death following differentiation with several factors such as fibroblast growth factor, constitutively activated Raf-1, or phorbol esters. The mechanism by which cell death occurs has not been identified. Using RNA differential display, we have identified and characterized a novel immediate early gene (denoted PQR for proline- and glutamine-rich) induced during differentiation of both rat hippocampal and septal cell lines. The 44-kDa PQR protein, rich in PQ, PH, and QQ repeats, is homologous to a murine protein (TDAG51) required for Fas-mediated apoptosis in T cells. To determine whether PQR acts as a mediator of apoptosis in neuronal cells, the hippocampal H19-7 cells were microinjected with either a plasmid expressing PQR cDNA or an antibody against PQR. Microinjection of differentiating H19-7 cells with a neutralizing antibody against PQR increased the number of surviving cells by 50%. Transient expression of PQR in both differentiating and nondifferentiating H19-7 cells decreased the number of surviving cells by 35-50%; this reduction was reversed by microinjection of PQR antibody. Finally, levels of Fas transcripts are not increased in the neuronal cells, indicating that the mechanism of action differs from that in T cells. These results demonstrate that PQR can be induced by growth factors and differentiating agents and can itself induce apoptosis in hippocampal H19-7 cells. Furthermore, these data suggest that PQR can function more generally as a mediator of apoptosis and provide a possible mechanism for induction of programmed cell death during neuronal development. |
| Databáze: | OpenAIRE |
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