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

FEBS Letters

Futai, Masamitsu²  Maeda, Masatomo¹  Nakagawa, Reiko¹  Sato, Ryuichiro¹  Yokosawa, Hideyoshi³ 

[1] Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565, Japan;Division of Biological Sciences, The Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka 567, Japan;Department of Biochemistry, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo 060, Japan

关键词: GATA factor;    DNA-binding protein;    Proteolysis;    Proteasome;    cAMP;    A kinase;    CHO;    Chinese hamster ovary;    dbcAMP;    dibutyryl cAMP;    dbcGMP;    dibutyryl cGMP;    DOG;    sn-1;    2-dioctanoylglycerol;    IP3;    d-myo-Inositol-1;    4;    5-triphosphate;    ECL;    enhanced chemiluminescence;    MG101;    N-acetyl-Leu-Leu-norleucinal;    MG115;    benzyloxycarbonyl-Leu-Leu-norvalinal;    TPA;    12-O-tetradecanoylphorbol 13-acetate;    PSI;    benzyloxycarbonyl-Ile-Glu(O-t-Bu)-Ala-leucinal;   

DOI  :  10.1016/S0014-5793(97)00443-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown