Repression of NF-kappaB impairs HeLa cell proliferation by functional interference with cell cycle checkpoint regulators

Oncogene. 1999 May 27;18(21):3213-25. doi: 10.1038/sj.onc.1202657.


NF-kappaB is an inducible transcription factor, which is regulated by interaction with inhibitory IkappaB proteins. Previous studies linked the activity of NF-kappaB to the proliferative state of the cell. Here we have analysed the function of NF-kappaB in the cell cycle. Inhibition of NF-kappaB in HeLa cells by stable overexpression of a transdominant negative IkappaB-alpha protein reduced cell growth. A kinetic analysis of the cell cycle revealed a retarded G1/S transition. The IkappaB-alpha overexpressing cell clones showed a decreased percentage of cells in the S phase and an impaired incorporation of bromodeoxyuridine (BrdU). The amounts of cyclins A, B1, D1, D3, and E were unchanged, but the G1-specific proteins cyclin D2 and cdk2 were strongly elevated in the IkappaB-alpha overexpressing cell clones. These cell clones also displayed an increase in cyclin D1-dependent kinase activity, pointing to a cell cycle arrest at the late G1 phase. IkappaB-alpha overexpression crosstalked to cell cycle checkpoints via a reduction of transcription factor p53 and elevation of p21WAF. Surprisingly, the IkappaB-alpha overexpressing cells showed an enrichment of c-Myc in the nucleoli, although the total amount of c-Myc protein was unchanged. These experiments identify an important contribution of the NF-kappaB/IkappaB system for the growth of HeLa cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle
  • Cell Division
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / metabolism*
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics
  • G1 Phase
  • Gene Expression
  • HeLa Cells
  • Humans
  • I-kappa B Proteins*
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-myc / metabolism*
  • S Phase
  • Signal Transduction*
  • Tumor Suppressor Protein p53 / metabolism*


  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • DNA-Binding Proteins
  • I-kappa B Proteins
  • NF-kappa B
  • NFKBIA protein, human
  • Proto-Oncogene Proteins c-myc
  • Tumor Suppressor Protein p53
  • NF-KappaB Inhibitor alpha