NAT10, a nucleolar protein, localizes to the midbody and regulates cytokinesis and acetylation of microtubules.
The midbody is a structural organelle formed in late phase mitosis which is responsible for completion of cytokinesis. Although various kinds of proteins have been found to distribute or immigrate to this organelle, their functions have still not been completely worked out. In this study, we demonstrated that NAT10 (N-acetyltransferase 10, NAT10) is not only predominantly distributed in the nucleolus in interphase, but is also concentrated in the mitotic midbody during telophase. The domain in N-terminal residues 549-834 of NAT10 specifically mediated its subcellular localization. Treatment with genotoxic agents or irradiation increased concentration of NAT10 in both the nucleolus and midbody. Moreover, DNA damage induced increase of NAT10 in the midbody apparently accompanied by in situ elevation of the level of acetylated alpha-tubulin, suggesting that it plays a role in maintaining or enhancing stability of alpha-tubulin. The depletion of NAT10 induced defects in nucleolar assembly, cytokinesis and decreased acetylated alpha-tubulin, leading to G2/M cell cycle arrest or delay of mitotic exit. In addition, over-expression of NAT10 was found in a variety of soft tissue sarcomas, and correlated with tumor histological grading. These results indicate that NAT10 may play an important role in cell division through facilitating reformation of the nucleolus and midbody in the late phase of cell mitosis, and stabilization of microtubules.
Shen
Qi
Q
Department of Pathology, Health Science Center of Peking University, Haidian District, Beijing, China.
Zheng
Xingzheng
X
McNutt
Michael A
MA
Guang
Lizhao
L
Sun
Ying
Y
Wang
Jiaochen
J
Gong
Yilei
Y
Hou
Lin
L
Zhang
Bo
B
D000107:Acetylation; D000123:Acetyltransferases / Q000737:chemistry / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D002466:Cell Nucleolus / Q000201:enzymology; D002648:Child; D002675:Child, Preschool; D048749:Cytokinesis; D004249:DNA Damage; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007223:Infant; D008870:Microtubules / Q000378:metabolism*; D008875:Middle Aged; D008938:Mitosis; D063213:N-Terminal Acetyltransferase E; D063206:N-Terminal Acetyltransferases; D009369:Neoplasms / Q000201:enzymology / Q000473:pathology; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D015388:Organelles / Q000201:enzymology*; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism; D015854:Up-Regulation
D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D014404:Tubulin; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D000123:Acetyltransferases; D063213:N-Terminal Acetyltransferase E; D063206:N-Terminal Acetyltransferases; C522989:NAT10 protein, human