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Caenorhabditis elegans protein arginine methyltransferase PRMT-5 negatively regulates DNA damage-induced apoptosis.
PLoS Genet. 2009 Jun; 5(6):e1000514.PG

Abstract

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.

Authors+Show Affiliations

Key Laboratory of Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19521535

Citation

Yang, Mei, et al. "Caenorhabditis Elegans Protein Arginine Methyltransferase PRMT-5 Negatively Regulates DNA Damage-induced Apoptosis." PLoS Genetics, vol. 5, no. 6, 2009, pp. e1000514.
Yang M, Sun J, Sun X, et al. Caenorhabditis elegans protein arginine methyltransferase PRMT-5 negatively regulates DNA damage-induced apoptosis. PLoS Genet. 2009;5(6):e1000514.
Yang, M., Sun, J., Sun, X., Shen, Q., Gao, Z., & Yang, C. (2009). Caenorhabditis elegans protein arginine methyltransferase PRMT-5 negatively regulates DNA damage-induced apoptosis. PLoS Genetics, 5(6), e1000514. https://doi.org/10.1371/journal.pgen.1000514
Yang M, et al. Caenorhabditis Elegans Protein Arginine Methyltransferase PRMT-5 Negatively Regulates DNA Damage-induced Apoptosis. PLoS Genet. 2009;5(6):e1000514. PubMed PMID: 19521535.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Caenorhabditis elegans protein arginine methyltransferase PRMT-5 negatively regulates DNA damage-induced apoptosis. AU - Yang,Mei, AU - Sun,Jianwei, AU - Sun,Xiaojuan, AU - Shen,Qinfang, AU - Gao,Zhiyang, AU - Yang,Chonglin, Y1 - 2009/06/12/ PY - 2009/01/12/received PY - 2009/05/12/accepted PY - 2009/6/13/entrez PY - 2009/6/13/pubmed PY - 2009/8/29/medline SP - e1000514 EP - e1000514 JF - PLoS genetics JO - PLoS Genet VL - 5 IS - 6 N2 - 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. SN - 1553-7404 UR - https://www.unboundmedicine.com/medline/citation/19521535/Caenorhabditis_elegans_protein_arginine_methyltransferase_PRMT_5_negatively_regulates_DNA_damage_induced_apoptosis_ L2 - https://dx.plos.org/10.1371/journal.pgen.1000514 DB - PRIME DP - Unbound Medicine ER -