Enhanced ribosomal association of p27(Kip1) mRNA is a mechanism contributing to accumulation during growth arrest

S. Sean Millard, Jie Shi Yan, Hoang Nguyen, Michele Pagano, Hiroaki Kiyokawa, Andrew Koff*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

170 Scopus citations

Abstract

p27(Kip1) regulates the decision to enter into S-phase or withdraw from the cell cycle by establishing an inhibitory threshold above which G1 cyclin-dependent kinases accumulate before activation. We have used the HL- 60 cell line to study regulation of p27 as cells withdraw from the cell cycle following treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA). We found that the amount of p27 is maximal in G0 cells, lower in G1 cells, and undetectable in S-phase cells. In contrast to the protein, the amount of p27 mRNA was the same in these populations, suggesting that accumulation of p27 during the cell cycle and as cells withdraw from the cell cycle is controlled by post-transcriptional mechanisms. In S-phase cells, the degradation of p27 appears to predominate as a regulatory mechanism. In G0 cells, there was an increase in the synthesis rate of p27. Our data demonstrate that, in G0 cells, accumulation of p27 is due to an increase in the amount of p27 mRNA in polyribosomes.

Original languageEnglish (US)
Pages (from-to)7093-7098
Number of pages6
JournalJournal of Biological Chemistry
Volume272
Issue number11
DOIs
StatePublished - Mar 14 1997

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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