CARM1 phosphorylation prevents interaction between PRMT1 and CARM1, two <> involved in proliferation in lung cancer

Abstract : PRMT1 and CARM1 are 2 Protein Arginine MethylTransferases (PRMTs) implicated in cell proliferation and deregulated in cancer. Dimerisation is a conserved feature in the PRMT family. PRMT1 and CARM1 cooperate in gene regulation but CARM1/PRMT1 heterodimer is not yet characterised. We report that, PRMT1 and CARM1 are overexpressed in non-small cell lung cancer samples and in 2 lung adenocarcinoma cell lines, A549 and H1299. siPRMT1 reduce proliferation and promote differentiation. siCARM1 yield similar consequences but, as this was previously described, suppress PRMT1 expression in addition to CARM1 expression. Thus CARM1 might reduce proliferation by a direct effect or alternatively through PRMT1 suppression. This result reinforces the interest of investigating the CARM1/PRMT1 heterodimer formation. We found that in A549 cells, CARM1 is not phosphorylated at serine 228, interacts with PRMT1, methylates the promoter of 2 target genes (Sox2 and Nanog) and is localized in the nucleus. In H1299 cells, CARM1 is phosphorylated at serine 228, does not interact with PRMT1, does not methylate Sox2 and Nanog promoters and is localized in the cytoplasm. Inhibition of the kinase MAP2K3 prevents the phosphorylation of CARM1 at serine 228 and restores CARM1/PRMT1 interaction in H1299 cells. In conclusion, we propose that PRMT1 knock-down reduces proliferation in lung cancer. CARM1 knock-down reduces proliferation probably through the suppression of PRMT1. We suggest that MAP2K3 is the candidate kinase that phosphorylates CARM1 at serine 228 and that phosphorylation inhibits CARM1/PRMT1 interaction. CARM1/PRMT1 heterodimer formation might be a way of regulating the activities of these enzymes
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Rania El Akoum. CARM1 phosphorylation prevents interaction between PRMT1 and CARM1, two <> involved in proliferation in lung cancer. Human health and pathology. Université de Lorraine, 2013. English. ⟨NNT : 2013LORR0128⟩. ⟨tel-01750121⟩

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