PRMT1 promotes mitosis of cancer cells through arginine methylation of INCENP

// Xiaolan Deng 1,2 , Gottfried Von Keudell 1 , Takehiro Suzuki 3 , Naoshi Dohmae 3 , Makoto Nakakido 1 , Lianhua Piao 1 , Yuichiro Yoshioka 1 , Yusuke Nakamura 1 and Ryuji Hamamoto 1 1 Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL, USA 2 Department of Pharmaceutical Analysis, School of Pharmacy, China Medical University, Shenyang, P. R. China 3 Biomolecular Characterization Unit, RIKEN Center for Sustainable Resource Science, Wako, Saitama, Japan Correspondence to: Ryuji Hamamoto, email: // Keywords : INCENP, Aurora kinase B, PRMT1, arginine methylation Received : August 20, 2015 Accepted : September 25, 2015 Published : October 09, 2015 Abstract Inner centromere protein (INCENP) is a part of a protein complex known as the chromosomal passenger complex (CPC) that is essential for correcting non-bipolar chromosome attachments and for cytokinesis. We here demonstrate that a protein arginine methyltransferase PRMT1, which are overexpressed in various types of cancer including lung and bladder cancer, methylates arginine 887 in an Aurora Kinase B (AURKB)-binding region of INCENP both in vitro and in vivo . R887-substituted INCENP revealed lower binding-affinity to AURKB than wild-type INCENP in the presence of PRMT1. Knockdown of PRMT1 as well as overexpression of methylation-inactive INCENP attenuated the AURKB activity in cancer cells, and resulted in abnormal chromosomal alignment and segregation. Furthermore, introduction of methylation-inactive INCENP into cancer cells reduced the growth rate, compared with those introduced wild-type INCENP or Mock. Our data unveils a novel mechanism of PRMT1-mediated CPC regulation through methylation of INCENP.