N-terminal transcriptional activation domain of LZIP comprises two LxxLL motifs and the host cell factor-1 binding motif

Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):10757-62. doi: 10.1073/pnas.190062797.

Abstract

Host Cell Factor-1 (HCF-1, C1) was first identified as a cellular target for the herpes simplex virus transcriptional activator VP16. Association between HCF and VP16 leads to the assembly of a multiprotein enhancer complex that stimulates viral immediate-early gene transcription. HCF-1 is expressed in all cells and is required for progression through G(1) phase of the cell cycle. In addition to VP16, HCF-1 associates with a cellular bZIP protein known as LZIP (or Luman). Both LZIP and VP16 contain a four-amino acid HCF-binding motif, recognized by the N-terminal beta-propeller domain of HCF-1. Herein, we show that the N-terminal 92 amino acids of LZIP contain a potent transcriptional activation domain composed of three elements: the HCF-binding motif and two LxxLL motifs. LxxLL motifs are found in a number of transcriptional coactivators and mediate protein-protein interactions, notably recognition of the nuclear hormone receptors. LZIP is an example of a sequence-specific DNA-binding protein that uses LxxLL motifs within its activation domain to stimulate transcription. The LxxLL motifs are not required for association with the HCF-1 beta-propeller and instead interact with other regions in HCF-1 or recruit additional cofactors.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Cell Line
  • Cyclic AMP Response Element-Binding Protein
  • Gene Expression Regulation, Viral
  • Herpes Simplex Virus Protein Vmw65 / genetics*
  • Herpes Simplex Virus Protein Vmw65 / metabolism
  • Host Cell Factor C1
  • Humans
  • Leucine Zippers
  • Molecular Sequence Data
  • Protein Binding
  • Proteins / genetics*
  • Proteins / metabolism
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Transcriptional Activation*

Substances

  • CREB3 protein, human
  • Cyclic AMP Response Element-Binding Protein
  • HCFC1 protein, human
  • Herpes Simplex Virus Protein Vmw65
  • Host Cell Factor C1
  • Proteins
  • Transcription Factors