Abstract
Protein arginine methyltransferases (PRMTs) catalyze the methylation of arginine residues on both histones and non-histone proteins. PRMT5, a member of the PRMT family, is overexpressed in a wide variety of cancers and its activity is associated with cell transformation. Moreover, its expression is associated with a decrease in patient survival in several cancers, a rationale for developing highly potent inhibitors of its enzymatic activity. However, most studies do not take into account the subcellular localization of PRMT5, which can modify its properties. Indeed, our team recently showed that PRMT5 nuclear expression is associated with prolonged survival. These results corroborated findings in prostate cancer, in which the nuclear fraction of PRMT5 was responsible for inhibiting cell growth, while the cytoplasmic fraction promoted cell growth. In conclusion, this criterion should be evaluated prior to administering PRMT5 inhibitors, which may have adverse effects.
Highlights
In this context, most studies have highlighted that PRMT5 overexpression is associated with a decrease in patient survival and an increase in ovarian, lung, multiple myeloma and breast tumor growth [4,5,6,7] (Figure 1A, 1B)
An increase in its activity is associated with cell transformation, exposing PRMT5 as a suitable druggable target for treating cancer [3]
This has been demonstrated for the protein encoded by the tumor suppressor gene LKB1, since its nuclear expression has been associated with increased survival in breast cancer, whereas its cytoplasmic expression is associated with a decrease in survival [9]
Summary
Most studies have highlighted that PRMT5 overexpression is associated with a decrease in patient survival and an increase in ovarian, lung, multiple myeloma and breast tumor growth [4,5,6,7] (Figure 1A, 1B). Arginine methylation is a frequent post-translational modification involved in various cellular processes, such as DNA transcription, mRNA splicing, signal transduction, protein interaction and subcellular protein localization [1, 2]. Members of the family are classified into three functional groups depending on the type of methylation they catalyze.
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