HCF-1 functions as a coactivator for the zinc finger protein Krox20

J Biol Chem. 2003 Dec 19;278(51):51116-24. doi: 10.1074/jbc.M303470200. Epub 2003 Oct 6.

Abstract

HCF-1 is a transcriptional cofactor required for activation of herpes simplex virus immediate-early genes by VP16 as well as less clearly defined roles in cell proliferation, cytokinesis, and spliceosome formation. It is expressed as a large precursor that undergoes proteolysis to yield two subunits that remain stably associated. VP16 uses a degenerate 4-amino acid sequence, known as the HCF-binding motif, to bind to a six-bladed beta-propeller domain at the N terminus of HCF-1. Functional HCF-binding motifs are also found in LZIP and Zhangfei, two cellular bZIP transcription factors of unknown function. Here we show that the HCF-binding motif occurs in a wide spectrum of DNA-binding proteins and transcriptional cofactors. Three well characterized examples were further analyzed for their ability to use HCF-1 as a coactivator. Krox20, a zinc finger transcription factor required for Schwann cell differentiation, and E2F4, a cell cycle regulator, showed a strong requirement for functional HCF-1 to activate transcription. In contrast, activation by estrogen receptor-alpha did not display HCF dependence. In Krox20, the HCF-binding motif lies within the N-terminal activation domain and mutation of this sequence diminishes both transactivation and association with the HCF-1 beta-propeller. The activation domain in the C-terminal subunit of HCF-1 contributes to activation by Krox20, possibly through recruitment of p300. These results suggest that HCF-1 is recruited by many different classes of cellular transcription factors and is therefore likely to be required for a variety of cellular processes including cell cycle progression and development.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Binding Sites
  • Cell Line
  • Consensus Sequence
  • DNA-Binding Proteins / metabolism
  • DNA-Binding Proteins / physiology*
  • E2F4 Transcription Factor
  • Early Growth Response Protein 2
  • Estrogen Receptor alpha
  • Host Cell Factor C1
  • Humans
  • Protein Binding
  • Protein Structure, Tertiary
  • Rats
  • Receptors, Estrogen / metabolism
  • Receptors, Estrogen / physiology
  • Temperature
  • Transcription Factors / metabolism
  • Transcription Factors / physiology*
  • Transfection
  • Zinc Fingers

Substances

  • DNA-Binding Proteins
  • E2F4 Transcription Factor
  • EGR2 protein, human
  • Early Growth Response Protein 2
  • Egr2 protein, rat
  • Estrogen Receptor alpha
  • HCFC1 protein, human
  • Host Cell Factor C1
  • Receptors, Estrogen
  • Transcription Factors