Caenorhabditis elegans protein arginine methyltransferase PRMT-5 negatively regulates DNA damage-induced apoptosis.
Arginine methylation of histone and non-histone proteins is involved in transcription regulation and many other cellular processes. Nevertheless, whether such protein modification plays a regulatory role during apoptosis remains largely unknown. Here we report that the Caenorhabditis elegans homolog of mammalian type II arginine methyltransferase PRMT5 negatively regulates DNA damage-induced apoptosis. We show that inactivation of C. elegans prmt-5 leads to excessive apoptosis in germline following ionizing irradiation, which is due to a CEP-1/p53-dependent up-regulation of the cell death initiator EGL-1. Moreover, we provide evidence that CBP-1, the worm ortholog of human p300/CBP, functions as a cofactor of CEP-1. PRMT-5 forms a complex with both CEP-1 and CBP-1 and can methylate the latter. Importantly, down-regulation of cbp-1 significantly suppresses DNA damage-induced egl-1 expression and apoptosis in prmt-5 mutant worms. These findings suggest that PRMT-5 likely represses CEP-1 transcriptional activity through CBP-1, which represents a novel regulatory mechanism of p53-dependent apoptosis.
Yang
Mei
M
Key Laboratory of Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
Sun
Jianwei
J
Sun
Xiaojuan
X
Shen
Qinfang
Q
Gao
Zhiyang
Z
Yang
Chonglin
C
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage / Q000528:radiation effects; D015536:Down-Regulation; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D011839:Radiation, Ionizing; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
C438244:CEP-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; C112486:EGL-1 protein, C elegans; D012097:Repressor Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D011484:Protein-Arginine N-Methyltransferases; C111709:CBP-1 protein, C elegans; D051548:Histone Acetyltransferases