MilliporeSigma
  • Arginine Methyltransferase PRMT1 Regulates p53 Activity in Breast Cancer.

Arginine Methyltransferase PRMT1 Regulates p53 Activity in Breast Cancer.

Life (Basel, Switzerland) (2021-08-28)
Li-Ming Liu, Qiang Tang, Xin Hu, Jing-Jing Zhao, Yuan Zhang, Guo-Guang Ying, Fei Zhang
ABSTRACT

The protein p53 is one of the most important tumor suppressors, responding to a variety of stress signals. Mutations in p53 occur in about half of human cancer cases, and dysregulation of the p53 function by epigenetic modifiers and modifications is prevalent in a large proportion of the remainder. PRMT1 is the main enzyme responsible for the generation of asymmetric-dimethylarginine, whose upregulation or aberrant splicing has been observed in many types of malignancies. Here, we demonstrate that p53 function is regulated by PRMT1 in breast cancer cells. PRMT1 knockdown activated the p53 signal pathway and induced cell growth-arrest and senescence. PRMT1 could directly bind to p53 and inhibit the transcriptional activity of p53 in an enzymatically dependent manner, resulting in a decrease in the expression levels of several key downstream targets of the p53 pathway. We were able to detect p53 asymmetric-dimethylarginine signals in breast cancer cells and breast cancer tissues from patients, and the signals could be significantly weakened by silencing of PRMT1 with shRNA, or inhibiting PRMT1 activity with a specific inhibitor. Furthermore, PRMT1 inhibitors significantly impeded cell growth and promoted cellular senescence in breast cancer cells and primary tumor cells. These results indicate an important role of PRMT1 in the regulation of p53 function in breast tumorigenesis.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
N-Acetyl-L-cysteine, suitable for cell culture, BioReagent
Sigma-Aldrich
Anti-PRMT1 Antibody, Upstate®, from rabbit
Sigma-Aldrich
SB 202190, ≥98% (HPLC)
Sigma-Aldrich
Monoclonal ANTI-FLAG® M2 antibody produced in mouse, clone M2, purified immunoglobulin (Purified IgG1 subclass), buffered aqueous solution (10 mM sodium phosphate, 150 mM NaCl, pH 7.4, containing 0.02% sodium azide)
Sigma-Aldrich
Anti-dimethyl-Arginine Antibody, asymmetric (ASYM25), serum, from rabbit
Sigma-Aldrich
Furamidine dihydrochloride, ≥98% (HPLC)