CARM1 (coactivator-associated arginine methyltransferase 1) belongs to a family of enzymes known as PRMTs (protein arginine methyltransferases), which can introduce arginine methylation. CARM1 is also referred to as PRMT4. Protein methylation, the addition of a methyl group to target proteins, is one type of post-translational modification that can change the function of the target proteins.
CARM1 has been reported to be overexpressed in breast cancer, and its overexpression is associated with high-grade tumors and poorer prognosis. So CARM1-specific inhibitors are considered a promising breast cancer therapy. However, until now only few targets of CARM1 have been identified, and how it recognizes these targets remains unclear.
Now, a team of researchers from the University of Wisconsin – Madison has mapped out the profile of CARM1 targets in breast cancer, by using the quantitative mass spectrometry. This may aid in the development of CARM1-spcific inhibitors for breast cancer treatment.
Study leader Prof. Wei Xu previously found two targets of CARM1: BAF155 and MED12. Additionally, CARM1-mediated BAF155 methylation correlates with breast cancer progression and metastasis. Other researchers include Evgenia Shishkova, Hao Zeng, Fabao Liu, Nicholas Kwiecien, Alexander Hebert, and Joshua Coon.
In this work, Xu's team employed multiple techniques including high-resolution mass spectrometry to globally profile CARM1 targets in two human breast cancer cell lines. They identified more than 300 CARM1-dependent arginine methylation events, and verified about 130 new CARM1 protein targets, many of which have cancer-related functions. Further, they also found that the N-terminus of CARM1 is necessary for target recognition and methylation. The researchers hypothesized that the design of CARM1-specific inhibitors should focus on the N-terminus of CARM1.
Overall, the study extends our knowledge of CARM1, provides insights into the working mechanism of other PRMTs, and opens up an avenue of drug discovery for breast cancer. Since CARM1 is also overexpressed in many other cancer types, the findings would have profound implications. (Cusabio offers CARM1, BAF155, MED12, and Recombinant fam171a2 proteins.)
The paper, "Global mapping of CARM1 substrates defines enzyme specificity and substrate recognition," appears in Nature Communications.
留言列表
