v-Abl protein-tyrosine kinase up-regulates p21WAF-1 in cell cycle arrested and proliferating myeloid cells

S J Khanna, R Brown, A D Whetton, K L Ball, C Dive

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

v-Abl protein-tyrosine kinase (PTK) promotes cell survival without cell proliferation in interleukin (IL)-3-deprived IC.DP premast cells (1). We now show that in these conditions v-Abl PTK transcriptionally up-regulated the cyclin-dependent kinase inhibitor (CDKI) p21(WAF-1) and inhibited CDK2 and CDK4. When readdition of IL-3 stimulated cell proliferation, p21(WAF-1) was inactivated as a CDKI despite maintenance of elevated protein level. p21(WAF-1) was also up-regulated yet was nonfunctional as a CDKI when v-Abl PTK was activated in cells maintained in IL-3, but this occurred without increased p21(WAF-1) transcription. Using a C-terminal epitope-specific p21(WAF-1) antibody, v-Abl PTK-mediated increase in p21(WAF-1) could be detected in intact cells only in the presence of IL-3. This indicated different binding partners of p21(WAF-1) and/or protein conformation in nondividing or proliferating cells, respectively. The binding of CDK2, CDK4, or proliferating cell nuclear antigen to p21(WAF-1) and its subcellular localization were unchanged in the presence or absence of IL-3. However, two-dimensional analysis revealed different forms of up-regulated p21(WAF-1) in IL-3-deprived, nondividing cells compared with IL-3-stimulated proliferating cells. These data demonstrate that elevation of the CDKI p21(WAF-1) is not always sufficient for cell cycle arrest and indicate an IL-3-sensitive pathway for the inactivation of p21(WAF-1) function as a CDKI.
Original languageEnglish
Pages (from-to)11143-50
Number of pages8
JournalJournal of Biological Chemistry
Issue number14
Publication statusPublished - 6 Apr 2001

Keywords / Materials (for Non-textual outputs)

  • Animals
  • Cell Cycle
  • Cell Division
  • Cell Line
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Genes, abl
  • Mast Cells
  • Mice
  • Mutation
  • Signal Transduction
  • Up-Regulation


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