A novel nucleolar protein, PAPA-1, induces growth arrest as a result of cell cycle arrest at the G1 phase

Gene. 2004 Sep 29;340(1):83-98. doi: 10.1016/j.gene.2004.05.025.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • BALB 3T3 Cells
  • Base Sequence
  • Blotting, Northern
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Carrier Proteins / physiology
  • Cell Cycle / physiology*
  • Cell Cycle Proteins
  • Cell Division / physiology
  • Cell Line
  • Cell Nucleolus / metabolism
  • Cell Nucleus / metabolism
  • Cloning, Molecular
  • DNA, Complementary / chemistry
  • DNA, Complementary / genetics
  • G1 Phase / physiology*
  • Gene Expression Profiling
  • HeLa Cells
  • Humans
  • L Cells
  • Male
  • Mice
  • Molecular Sequence Data
  • Mutation
  • NIH 3T3 Cells
  • Nuclear Localization Signals / genetics
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Nuclear Proteins / physiology
  • Pancreatitis-Associated Proteins
  • Protein Binding
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sequence Alignment
  • Sequence Analysis, DNA
  • Sequence Homology, Amino Acid
  • Transfection


  • Carrier Proteins
  • Cell Cycle Proteins
  • DNA, Complementary
  • INO80B protein, human
  • Nuclear Localization Signals
  • Nuclear Proteins
  • PAPA-1 protein, mouse
  • Pancreatitis-Associated Proteins
  • REG3A protein, human
  • RNA, Messenger

Associated data

  • GENBANK/AB054537
  • GENBANK/AB054538