TY - JOUR
T1 - Arginine methylation of ubiquitin-associated protein 2-like is required for the accurate distribution of chromosomes
AU - Maeda, Masao
AU - Hasegawa, Hitoki
AU - Sugiyama, Mai
AU - Hyodo, Toshinori
AU - Ito, Satoko
AU - Chen, Dan
AU - Asano, Eri
AU - Masuda, Akio
AU - Hasegawa, Yoshinori
AU - Hamaguchi, Michinari
AU - Senga, Takeshi
N1 - Funding Information:
The authors thank the members of the Division of Cancer Biology for technical assistance and helpful discussions. This research was funded by Grants 25650063 and 2306 from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (to T.S.).
Publisher Copyright:
© FASEB.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - Proper bioriented attachment of microtubules and kinetochores is essential for the precise distribution of duplicated chromosomes to each daughter cell. An aberrant kinetochore-microtubule attachment results in chromosome instability, which leads to cellular transformation or apoptosis. In this article, we show that ubiquitin-associated protein 2-like (UBAP2L) is necessary for correct kinetochore-microtubule attachment. Depletion of UBAP2L inhibited chromosome alignment in metaphase and delayed progression to anaphase by activating spindle assembly checkpoint signaling. In addition, UBAP2L knockdown increased side-on attachment of kinetochores along the microtubules and suppressed stable kinetochore fiber formation. A proteomics analysis identified protein arginine methyltransferase (PRMT)1 as a direct interaction partner of UBAP2L. UBAP2L has an arginine- and glycine-rich motif called the RGG/RG or GAR motif in the N terminus. Biochemical analysis confirmed that arginine residues in the RGG/RG motif of UBAP2L were directly methylated by PRMT1. Finally, we demonstrated that the RGG/RG motif of UBAP2L is essential for the proper alignment of chromosomes in metaphase for the accurate distribution of chromosomes. Our results show a possible role for arginine methylation in UBAP2L for the progression of mitosis.
AB - Proper bioriented attachment of microtubules and kinetochores is essential for the precise distribution of duplicated chromosomes to each daughter cell. An aberrant kinetochore-microtubule attachment results in chromosome instability, which leads to cellular transformation or apoptosis. In this article, we show that ubiquitin-associated protein 2-like (UBAP2L) is necessary for correct kinetochore-microtubule attachment. Depletion of UBAP2L inhibited chromosome alignment in metaphase and delayed progression to anaphase by activating spindle assembly checkpoint signaling. In addition, UBAP2L knockdown increased side-on attachment of kinetochores along the microtubules and suppressed stable kinetochore fiber formation. A proteomics analysis identified protein arginine methyltransferase (PRMT)1 as a direct interaction partner of UBAP2L. UBAP2L has an arginine- and glycine-rich motif called the RGG/RG or GAR motif in the N terminus. Biochemical analysis confirmed that arginine residues in the RGG/RG motif of UBAP2L were directly methylated by PRMT1. Finally, we demonstrated that the RGG/RG motif of UBAP2L is essential for the proper alignment of chromosomes in metaphase for the accurate distribution of chromosomes. Our results show a possible role for arginine methylation in UBAP2L for the progression of mitosis.
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U2 - 10.1096/fj.14-268987
DO - 10.1096/fj.14-268987
M3 - Article
C2 - 26381755
AN - SCOPUS:84973474091
SN - 0892-6638
VL - 30
SP - 312
EP - 323
JO - FASEB Journal
JF - FASEB Journal
IS - 1
ER -