%0 Journal Article
%T SHARPIN-mediated regulation of protein arginine methyltransferase 5 controls melanoma growth
%A Ayako Murao
%A Hao Zhang
%A Harriet Kluger
%A Heejung Kim
%A Hironari Tamiya
%A Hyungsoo Kim
%A Jee Yun Han
%A Kazuhiro Iwai
%A Kevin Brown
%A Lucia Jilaveanu
%A Oleksiy Klymenko
%A Scott J. Snipas
%A Tongwu Zhang
%A Yongmei Feng
%A ZeˇŻev A. Ronai
%J The Journal of Clinical Investigation
%D 2018
%R 10.1172/JCI95410
%X SHARPIN, an adaptor for the linear ubiquitin chain assembly complex (LUBAC), plays important roles in NF-¦ĘB signaling and inflammation. Here, we have demonstrated a LUBAC-independent role for SHARPIN in regulating melanoma growth. We observed that SHARPIN interacted with PRMT5, a type II protein arginine methyltransferase, and increased its multiprotein complex and methyltransferase activity. Activated PRMT5 controlled the expression of the transcription factors SOX10 and MITF by SHARPIN-dependent arginine dimethylation and inhibition of the transcriptional corepressor SKI. Activation of PRMT5 by SHARPIN counteracted PRMT5 inhibition by methylthioadenosine, a substrate of methylthioadenosine phosphorylase, which is codeleted with cyclin-dependent kinase inhibitor 2A (CDKN2A) in approximately 15% of human cancers. Collectively, we identified a LUBAC-independent role for SHARPIN in enhancing PRMT5 activity that contributes to melanomagenesis through the SKI/SOX10 regulatory axis
%U https://www.jci.org/articles/view/95410