The histone gene transcription factor HiNF-P stabilizes its cell cycle regulatory co-activator p220NPAT

Biochemistry. 2006 Dec 26;45(51):15915-20. doi: 10.1021/bi061425m.


Orderly progression through the cell cycle requires the transcriptional activation of histone genes to support packaging of newly replicated DNA. Induction of human histone gene expression is mediated by a co-activation complex containing transcription factor HiNF-P and its cofactor p220NPAT. Here, using cells synchronized in S-phase and in mitosis, as well as serum-stimulated cells, we have investigated how HiNF-P is regulated during the cell cycle and examined its stability relative to p220NPAT. We find that while HiNF-P is maintained at steady-state levels throughout the cell cycle, both HiNF-P and p220NPAT are actively degraded by the proteasome pathway. Importantly, elevation of HiNF-P levels enhances the stability of its co-activator p220NPAT. The HiNF-P-dependent stabilization of p220NPAT may reinforce signaling through the cyclin E/CDK2/p220NPAT pathway and contribute to coordinate control of histone gene expression.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Cycle Proteins / metabolism*
  • Cell Cycle Proteins / physiology
  • Cell Cycle* / genetics
  • Cyclin E / physiology
  • Cyclin-Dependent Kinase 2 / physiology
  • Half-Life
  • HeLa Cells
  • Histones / genetics*
  • Histones / metabolism*
  • Humans
  • Nuclear Proteins / metabolism*
  • Nuclear Proteins / physiology
  • Proteasome Endopeptidase Complex / physiology
  • RNA, Messenger / metabolism
  • Repressor Proteins / biosynthesis
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Repressor Proteins / physiology*
  • Signal Transduction / genetics
  • Trans-Activators / metabolism*
  • Trans-Activators / physiology
  • Ubiquitin-Protein Ligase Complexes / physiology


  • Cell Cycle Proteins
  • Cyclin E
  • HINFP protein, human
  • Histones
  • NPAT protein, human
  • Nuclear Proteins
  • RNA, Messenger
  • Repressor Proteins
  • Trans-Activators
  • Ubiquitin-Protein Ligase Complexes
  • Cyclin-Dependent Kinase 2
  • Proteasome Endopeptidase Complex