A novel nucleolar protein, PAPA-1, induces growth arrest as a result of cell cycle arrest at the G1 phase.
We have identified a novel nucleolar protein, PAP-1-associated protein-1 (PAPA-1), after screening the interacting proteins with Pim-1-associated protein-1 (PAP-1), a protein that is a phosphorylation target of Pim-1 kinase. PAPA-1 comprises 345 amino acids with a basic amino-acid cluster. PAPA-1 was found to be localized in the nucleolus in transfected HeLa cells, and the lysine/histidine cluster was essential for nucleolar localization of PAPA-1. PAPA-1 protein and mRNA expression decreased upon serum restimulation of starvation-synchronized cells, which displayed maximum level of PAPA-1 expression at G0 and early G1 phase of the cell cycle. Ectopic expression of PAPA-1 induced growth suppression of cells, and the effect was dependent on its nucleolar localization in established HeLa cell lines that inducibly express PAPA-1 or its deletion mutant under the control of a tetracycline-inducible promoter. Furthermore, when PAPA-1-inducible HeLa cells were synchronized by thymidine, colcemid or mimosine, and then PAPA-1 was expressed, the proportion of cells at the G1 phase was obviously increased. These results suggest that PAPA-1 induces growth and cell cycle arrests at the G1 phase of the cell cycle.
Kuroda
Taruho S
TS
Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita, Sapporo 060-0812, Japan.
Maita
Hiroshi
H
Tabata
Takanori
T
Taira
Takahiro
T
Kitaura
Hirotake
H
Ariga
Hiroyoshi
H
Iguchi-Ariga
Sanae M M
SM
D000595:Amino Acid Sequence; D000818:Animals; D041702:BALB 3T3 Cells; D001483:Base Sequence; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D002466:Cell Nucleolus / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D016193:G1 Phase / Q000502:physiology*; D020869:Gene Expression Profiling; D006367:HeLa Cells; D006801:Humans; D007739:L Cells; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D041681:NIH 3T3 Cells; D019913:Nuclear Localization Signals / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D000073718:Pancreatitis-Associated Proteins; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014162:Transfection
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D018076:DNA, Complementary; C494434:INO80B protein, human; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins; C494435:PAPA-1 protein, mouse; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human; D012333:RNA, Messenger