title: A putative N-terminal nuclear export sequence is sufficient for Mps1 nuclear exclusion during interphase.
abstract: BACKGROUND
  Mps1, an essential component of the mitotic checkpoint, is also an important interphase regulator and has roles in DNA damage response, cytokinesis and centrosome duplication. Mps1 predominantly resides in the cytoplasm and relocates into the nucleus at the late G2 phase. So far, the mechanism underlying the Mps1 translocation between the cytoplasm and nucleus has been unclear.
  
  
  RESULTS
  In this work, a dynamic export process of Mps1 from the nucleus to cytoplasm in interphase was revealed- a process blocked by the Crm1 inhibitor, Leptomycin B, suggesting that export of Mps1 is Crm1 dependent. Consistent with this speculation, a direct association between Mps1 and Crm1 was found. Furthermore, a putative nuclear export sequence (pNES) motif at the N-terminal of Mps1 was identified by analyzing the motif of Mps1. This motif shows a high sequence similarity to the classic NES, a fusion of this motif with EGFP results in dramatic exclusion of the fusion protein from the nucleus. Additionally, Mps1 mutant loss of pNES integrity was shown by replacing leucine with alanine which produced a diffused subcellular distribution, compared to the wild type protein which resides predominantly in cytoplasm.
  
  
  CONCLUSIONS
  Taken these findings together, it was concluded that the pNES sequence is sufficient for the Mps1 export from nucleus during interphase.
authors.affiliation: Navy General Hospital of China, Beijing, 100048, China. 13321120266@126.com.
authors.forename: Haiwei
authors.initials: H
authors.lastname: Jia
authors.affiliation: State Key Laboratory for Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China. xjzhang@genetics.ac.cn.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Beijing Institute of Biotechnology, Taiping road 27, POB 130(8), Beijing, 100850, China. wangwenjun0602@163.com.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Wang
authors.affiliation: Beijing Institute of Biotechnology, Taiping road 27, POB 130(8), Beijing, 100850, China. 18210018092@163.com.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Beijing Institute of Biotechnology, Taiping road 27, POB 130(8), Beijing, 100850, China. 576482506@qq.com.|Department of Life Science, Anhui University, Hefei, 230601, China. 576482506@qq.com.
authors.forename: Youguo
authors.initials: Y
authors.lastname: Ling
authors.affiliation: Beijing Institute of Biotechnology, Taiping road 27, POB 130(8), Beijing, 100850, China. caoc@nic.bmi.ac.cn.
authors.forename: Cheng
authors.initials: C
authors.lastname: Cao
authors.affiliation: State Key Laboratory for Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China. rlma@genetics.ac.cn.
authors.forename: Runlin Z
authors.initials: RZ
authors.lastname: Ma
authors.affiliation: Beijing Institute of Biotechnology, Taiping road 27, POB 130(8), Beijing, 100850, China. towall@yahoo.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhong
authors.affiliation: West China Hospital, Sichuan University, Chengdu, 610041, China. zwangxue73@yahoo.com.
authors.forename: Xue
authors.initials: X
authors.lastname: Wang
authors.affiliation: Beijing Institute of Biotechnology, Taiping road 27, POB 130(8), Beijing, 100850, China. xuquanbin73@yahoo.com.
authors.forename: Quanbin
authors.initials: Q
authors.lastname: Xu
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D020816:Amino Acid Motifs; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D007399:Interphase; D028884:Karyopherins / Q000037:antagonists & inhibitors / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000378:metabolism; D000097606:Exportin 1 Protein
chemical_list: D018797:Cell Cycle Proteins; D005231:Fatty Acids, Unsaturated; D028884:Karyopherins; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D018160:Receptors, Cytoplasmic and Nuclear; D000097606:Exportin 1 Protein; C075840:TTK protein, human; C038753:leptomycin B