Gastric GATA-6 DNA-binding protein: proteolysis induced by cAMP.
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.
Nakagawa
R
R
Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Osaka University, Suita, Japan.
Sato
R
R
Futai
M
M
Yokosawa
H
H
Maeda
M
M
D000595:Amino Acid Sequence; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology*; D016466:CHO Cells; D002772:Cholera Toxin / Q000494:pharmacology; D017124:Conserved Sequence; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism*; D004268:DNA-Binding Proteins; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D004075:Diglycerides / Q000494:pharmacology; D019084:Fluorescent Antibody Technique, Indirect; D050993:GATA6 Transcription Factor; D005753:Gastric Mucosa / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D007700:Kinetics; D007976:Leupeptins / Q000494:pharmacology; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology; D011335:Proadifen / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors; D014162:Transfection; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D004075:Diglycerides; D050993:GATA6 Transcription Factor; D007976:Leupeptins; D009842:Oligopeptides; D011480:Protease Inhibitors; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C090535:benzyloxycarbonyl-isoleucyl-glutamyl(O-tert-butyl)-alanyl-leucinal; C089486:carbobenzoxy-leucyl-leucyl-norvalinal; D003995:Dibutyryl Cyclic GMP; D003994:Bucladesine; D015544:Inositol 1,4,5-Trisphosphate; D002772:Cholera Toxin; D011335:Proadifen; D000242:Cyclic AMP; D013755:Tetradecanoylphorbol Acetate; C013965:diolein