Misregulated RNA Pol II C-terminal domain phosphorylation results in apoptosis.
Misregulation of the level of RNA polymerase II carboxyl-terminal domain (CTD) phosphatase, Fcp1, in Drosophila results in high level of caspase-mediated apoptosis. Apoptosis induction by Fcp1 misregulation requires the presence of Drosophila melanogaster (Dm)p53, but occurs without the transcriptional activation of Dmp53 proapoptotic targets rpr, ark, and hid. Overproduction of a transcription activation-defective mutant Dmp53 protein increases, while Dmp53 null background decreases significantly the level of apoptosis in Fcp1-misregulated animals. Generating the apoptotic signal does not require the function of the ATM and Rad3-related kinase (ATR), and no significant level of nucleo-cytoplasmic translocation of Dmp53 is detectable in cells expressing Fcp1 at an abnormal level. Immunostaining of larval salivary gland polytene chromosomes with anti-Dmp53 antibodies indicates Dmp53 localization at several transcriptionally active chromosomal regions in wild-type cells, while in Fcp-misregulated cells the association of Dmp53 with specific chromosomal sites is decreased.
Schauer
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Chromatin Research Group of HAS, Department of Biochemistry and Molecular Biology, University of Szeged, Közép fasor 52, 6726 Szeged, Hungary.
Tombácz
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I
Ciurciu
A
A
Komonyi
O
O
Boros
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IM
D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000502:physiology*; D020169:Caspases / Q000378:metabolism; D002875:Chromosomes / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000033:anatomy & histology / Q000235:genetics* / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism; D019076:Transgenes; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D029721:Drosophila Proteins; D016159:Tumor Suppressor Protein p53; D012319:RNA Polymerase II; C539320:Fcp1 protein, Drosophila; D010749:Phosphoprotein Phosphatases; D020169:Caspases