PMID- 22987071
OWN - NLM
STAT- MEDLINE
DCOM- 20130114
LR  - 20211021
IS  - 1362-4962 (Electronic)
IS  - 0305-1048 (Print)
IS  - 0305-1048 (Linking)
VI  - 40
IP  - 19
DP  - 2012 Oct
TI  - p53-Independent regulation of p21Waf1/Cip1 expression and senescence by PRMT6.
PG  - 9534-42
LID - 10.1093/nar/gks858 [doi]
AB  - 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.
FAU - Phalke, Sameer
AU  - Phalke S
AD  - Division of Cancer Genetics and Therapeutics, Institute of Molecular and Cell 
      Biology, A*STAR (Agency for Science, Technology and Research), Singapore 138673.
FAU - Mzoughi, Slim
AU  - Mzoughi S
FAU - Bezzi, Marco
AU  - Bezzi M
FAU - Jennifer, Nancy
AU  - Jennifer N
FAU - Mok, Wei Chuen
AU  - Mok WC
FAU - Low, Diana H P
AU  - Low DH
FAU - Thike, Aye Aye
AU  - Thike AA
FAU - Kuznetsov, Vladimir A
AU  - Kuznetsov VA
FAU - Tan, Puay Hoon
AU  - Tan PH
FAU - Voorhoeve, P Mathijs
AU  - Voorhoeve PM
FAU - Guccione, Ernesto
AU  - Guccione E
LA  - eng
PT  - Journal Article
DEP - 20120916
PL  - England
TA  - Nucleic Acids Res
JT  - Nucleic acids research
JID - 0411011
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 2.1.1.319 (PRMT6 protein, human)
RN  - EC 2.1.1.319 (Protein-Arginine N-Methyltransferases)
SB  - IM
MH  - Animals
MH  - Breast Neoplasms/*genetics/metabolism/pathology
MH  - Cell Cycle Checkpoints
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Cellular Senescence
MH  - Cyclin-Dependent Kinase Inhibitor p21/*genetics
MH  - Female
MH  - *Gene Expression Regulation, Neoplastic
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - Mice
MH  - Mice, SCID
MH  - Nuclear Proteins/genetics/*metabolism
MH  - Phenotype
MH  - Promoter Regions, Genetic
MH  - Protein-Arginine N-Methyltransferases/genetics/*metabolism
MH  - Repressor Proteins/*metabolism
MH  - Tumor Suppressor Protein p53/metabolism
PMC - PMC3479215
EDAT- 2012/09/19 06:00
MHDA- 2013/01/15 06:00
PMCR- 2012/09/16
CRDT- 2012/09/19 06:00
PHST- 2012/09/19 06:00 [entrez]
PHST- 2012/09/19 06:00 [pubmed]
PHST- 2013/01/15 06:00 [medline]
PHST- 2012/09/16 00:00 [pmc-release]
AID - gks858 [pii]
AID - 10.1093/nar/gks858 [doi]
PST - ppublish
SO  - Nucleic Acids Res. 2012 Oct;40(19):9534-42. doi: 10.1093/nar/gks858. Epub 2012 
      Sep 16.