Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/98603
Title: p53-independent regulation of p21Waf1/Cip1 expression and senescence by PRMT6
Authors: Phalke, Sameer
Mzoughi, Slim
Bezzi, Marco
Jennifer, Nancy
Mok, Wei Chuen
Thike, Aye Aye
Tan, Puay Hoon
Voorhoeve, P. Mathijs
Guccione, Ernesto
Low, Diana H. P.
Kuznetsov, Vladimir A.
Keywords: DRNTU::Engineering::Computer science and engineering
Issue Date: 2012
Source: Phalke, S., Mzoughi, S., Bezzi, M., Jennifer, N., Mok, W. C., Low, D. H. P., et al. (2012). p53-Independent regulation of p21Waf1/Cip1 expression and senescence by PRMT6. Nucleic Acids Research, 40(19), 9534-9542.
Series/Report no.: Nucleic acids research
Abstract: p21 is a potent cyclin-dependent kinase inhibitor that plays a role in promoting G1 cell cycle arrest and cellular senescence. Consistent with this role, p21 is a downstream target of several tumour suppressors and oncogenes, and it is downregulated in the majority of tumours, including breast cancer. Here, we report that protein arginine methyltransferase 6 (PRMT6), a type I PRMT known to act as a transcriptional cofactor, directly represses the p21 promoter. PRMT6 knock-down (KD) results in a p21 derepression in breast cancer cells, which is p53-independent, and leads to cell cycle arrest, cellular senescence and reduced growth in soft agar assays and in severe combined immunodeficiency (SCID) mice for all the cancer lines examined. We finally show that bypassing the p21-mediated arrest rescues PRMT6 KD cells from senescence, and it restores their ability to grow on soft agar. We conclude that PRMT6 acts as an oncogene in breast cancer cells, promoting growth and preventing senescence, making it an attractive target for cancer therapy.
URI: https://hdl.handle.net/10356/98603
http://hdl.handle.net/10220/10920
ISSN: 0305-1048
DOI: 10.1093/nar/gks858
Rights: © 2012 The Author(s) (Published by Oxford University Press). This paper was published in Nucleic Acids Research and is made available as an electronic reprint (preprint) with permission of The Author(s) (Published by Oxford University Press). The paper can be found at the following official DOI: [http://dx.doi.org/10.1093/nar/gks858]. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SCSE Journal Articles

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