The estrogen-responsive B box protein: a novel regulator of keratinocyte differentiation

J Biol Chem. 2002 Jun 7;277(23):20740-9. doi: 10.1074/jbc.M111233200. Epub 2002 Mar 27.


Keratinocyte growth factor (KGF) regulates proliferation, differentiation, migration, and survival of different types of epithelial cells, including keratinocytes of the skin. To gain insight into the mechanisms underlying these multiple functions, we searched for KGF- regulated genes in keratinocytes. Using the differential display reverse transcriptase-PCR technology, we identified the gene encoding the estrogen-responsive B box protein (EBBP) which has as yet not been functionally characterized. The full-length murine and human EBBP cDNAs were cloned and fully sequenced. They were shown to encode 75-kDa proteins, which are mainly localized in the cytoplasm of keratinocytes in vitro and in vivo. In vivo, EBBP was found at high levels in the KGF- and epidermal growth factor-responsive basal keratinocytes of human skin, but the expression was down-regulated in the hyperthickened epithelium of skin wounds. Stable overexpression of EBBP in HaCaT keratinocytes did not affect the proliferation rate of the transfected cells, but enhanced the early differentiation process. These results suggest that the presence of EBBP in basal keratinocytes is important for the differentiation capacity of these cells, and that down-regulation of EBBP expression in a hyperproliferative epithelium is required to maintain the cells in a non-differentiated stage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Blood
  • Cell Differentiation / physiology*
  • Cell Line
  • Cloning, Molecular
  • DNA, Complementary
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Epidermal Growth Factor / physiology
  • Estrogens / physiology*
  • Fibroblast Growth Factor 7
  • Fibroblast Growth Factors / physiology
  • Fluorescent Antibody Technique, Indirect
  • Humans
  • Keratinocytes / cytology*
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Skin / metabolism
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Tripartite Motif Proteins
  • Ubiquitin-Protein Ligases
  • Wound Healing


  • DNA, Complementary
  • DNA-Binding Proteins
  • Estrogens
  • FGF7 protein, human
  • Fgf7 protein, mouse
  • Transcription Factors
  • Tripartite Motif Proteins
  • Fibroblast Growth Factor 7
  • Fibroblast Growth Factors
  • Epidermal Growth Factor
  • TRIM16 protein, human
  • Ubiquitin-Protein Ligases

Associated data

  • GENBANK/AF449496