PMID:22952863

Citation	Gu, Z, Li, Y, Lee, P, Liu, T, Wan, C and Wang, Z (2012) Protein arginine methyltransferase 5 functions in opposite ways in the cytoplasm and nucleus of prostate cancer cells. PLoS ONE 7:e44033
Abstract	Protein arginine methyltransferase 5 (PRMT5) plays multiple roles in a large number of cellular processes, and its subcellular localization is dynamically regulated during mouse development and cellular differentiation. However, little is known of the functional differences between PRMT5 in the cytoplasm and PRMT5 in the nucleus. Here, we demonstrated that PRMT5 predominantly localized in the cytoplasm of prostate cancer cells. Subcellular localization assays designed to span the entire open-reading frame of the PRMT5 protein revealed the presence of three nuclear exclusion signals (NESs) in the PRMT5 protein. PRMT5 and p44/MED50/WD45/WDR77 co-localize in the cytoplasm, and both are required for the growth of prostate cancer cells in an PRMT5 methyltransferase activity-dependent manner. In contrast, PRMT5 in the nucleus inhibited cell growth in a methyltransferase activity-independent manner. Consistent with these observations, PRMT5 localized in the nucleus in benign prostate epithelium, whereas it localized in the cytoplasm in prostate premalignant and cancer tissues. We further found that PRMT5 alone methylated both histone H4 and SmD3 proteins but PRMT5 complexed with p44 and pICln methylated SmD3 but not histone H4. These results imply a novel mechanism by which PRMT5 controls cell growth and contributes to prostate tumorigenesis.
Links	PubMed PMC3428323 Online version:10.1371/journal.pone.0044033
Keywords	Amino Acid Sequence; Animals; COS Cells; Cell Line, Tumor; Cell Nucleus/enzymology; Cell Proliferation; Cercopithecus aethiops; Gene Silencing; Humans; Male; Mice; Molecular Sequence Data; Nuclear Localization Signals; Prostatic Neoplasms/enzymology; Prostatic Neoplasms/pathology; Protein Binding; Protein Transport; Protein-Arginine N-Methyltransferases/chemistry; Protein-Arginine N-Methyltransferases/metabolism; Subcellular Fractions/enzymology; Substrate Specificity; Transcription Factors/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:ANM5		GO:0005737: cytoplasm	ECO:0000314:		C		Figure 1 shows PRMT5 localized in the cytoplasm	complete CACAO 7853
HUMAN:ANM5	part_of	GO:0005737: cytoplasm	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete

References

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