Gastric GATA-6 DNA-binding protein: proteolysis induced by cAMP

FEBS Lett. 1997 May 26;408(3):301-5. doi: 10.1016/s0014-5793(97)00443-2.


The rat gastric GATA DNA-binding protein, GATA-6 (GATA-GT1), was stably expressed in CHO-K1 cells. The GATA-6 protein was localized in the nucleus but not in the cytoplasm. Interestingly, when cells were treated with dibutyryl cAMP, the GATA-6 protein was specifically degraded. Such a phenomenon was not observed in the presence of 5'-AMP or dibutyryl cGMP. The cellular level of the GATA-6 protein was restored upon removal of dibutyryl cAMP. Degradation was also induced by cholera toxin, which increased the cellular cAMP concentration, and was inhibited by a protein kinase A inhibitor. However, activators of protein kinase C did not have any effect. The degradation was inhibited by proteasome inhibitors (PSI (benzyloxycarbonyl-Ile-Glu(O-t-Bu)-Ala-leucinal) and MG115 (benzyloxycarbonyl-Leu-Leu-norvalinal)) but not by those of lysosomes and serine proteases. These results suggest that a kinase-mediated protein phosphorylation is the cellular signal for degradation of the GATA-6 protein. This finding constitutes a novel aspect of regulation by GATA DNA-binding proteins, which are essential for developmental processes and tissue-specific transcription.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bucladesine / pharmacology*
  • CHO Cells
  • Cholera Toxin / pharmacology
  • Conserved Sequence
  • Cricetinae
  • Cyclic AMP / metabolism*
  • DNA-Binding Proteins
  • Dibutyryl Cyclic GMP / pharmacology
  • Diglycerides / pharmacology
  • Fluorescent Antibody Technique, Indirect
  • GATA6 Transcription Factor
  • Gastric Mucosa / metabolism
  • Inositol 1,4,5-Trisphosphate / pharmacology
  • Kinetics
  • Leupeptins / pharmacology
  • Molecular Sequence Data
  • Oligopeptides / pharmacology
  • Proadifen / pharmacology
  • Protease Inhibitors / pharmacology
  • Rats
  • Recombinant Fusion Proteins / metabolism
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transcription Factors
  • Transfection
  • Zinc Fingers


  • DNA-Binding Proteins
  • Diglycerides
  • GATA6 Transcription Factor
  • Leupeptins
  • Oligopeptides
  • Protease Inhibitors
  • Recombinant Fusion Proteins
  • Transcription Factors
  • benzyloxycarbonyl-isoleucyl-glutamyl(O-tert-butyl)-alanyl-leucinal
  • carbobenzoxy-leucyl-leucyl-norvalinal
  • Dibutyryl Cyclic GMP
  • Bucladesine
  • Inositol 1,4,5-Trisphosphate
  • Cholera Toxin
  • Proadifen
  • Cyclic AMP
  • Tetradecanoylphorbol Acetate
  • diolein