Molecular cloning and expression analysis of human glycogen synthase kinase-3 alpha promoter

Brain Res Mol Brain Res. 2000 Dec 8;84(1-2):150-7. doi: 10.1016/s0169-328x(00)00238-2.


Human glycogen synthase kinase-3 alpha (GSK-3 alpha) is a serine/threonine kinase that phosphorylates a variety of cytoplasmic and nuclear proteins. It also phosphorylates components of the neuronal cytoskeleton including tau and neurofilament heavy chain. Hyperphosphorylated tau is found in neurofibrillary tangles, a hallmark of Alzheimer's disease and aberrant phosphorylation of neurofilament heavy chain is observed in motor neuron disease. Alterations in GSK-3 alpha activity may therefore contribute to the disease process in these disorders. As a first step to understand the transcriptional regulation of GSK-3 alpha, a 2-kb (p-1751/+243) DNA fragment upstream of the GSK-3 alpha initiation codon was obtained from a YAC clone and characterised. Using primer extension assays, a putative transcriptional start site was located to a G nucleotide 244 bp upstream of the ATG codon. Several transcription factor-binding sites were identified on the promoter region, but no TATA-like element was located close to the start site. Deletion mutants of the 2-kb DNA fragment were generated and fused to a promoterless chloramphenicol acetyltransferase (CAT) gene. Transfection study in a neuroblastoma cell line revealed the 1-kb (p-719/+243) fragment carried strong promoter activity, while the 2-kb construct that contains an Alu-like sequence was only 50% active.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alu Elements / genetics
  • Base Sequence
  • Calcium-Calmodulin-Dependent Protein Kinases / genetics*
  • Chromosomes, Artificial, Yeast / genetics
  • Cloning, Molecular
  • Gene Expression Regulation*
  • Genes, Reporter
  • Glycogen Synthase Kinase 3
  • Glycogen Synthase Kinases
  • Humans
  • Molecular Sequence Data
  • Promoter Regions, Genetic / genetics*
  • Protein Subunits
  • Sequence Deletion / genetics
  • TATA Box / genetics
  • Transfection
  • Tumor Cells, Cultured


  • Protein Subunits
  • Glycogen Synthase Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Glycogen Synthase Kinase 3

Associated data

  • GENBANK/AC006486
  • GENBANK/AF115250
  • GENBANK/L40027