15?Deoxy?? <sup>12,14</sup> ?prostaglandin J <sub>2</sub> binds and inactivates STAT3 <i>via</i> covalent modification of cysteine 259 in H? <i>Ras</i> ?transformed human breast epithelial cells
نویسندگان
چکیده
Signal transducer and activator of transcription 3 (STAT3) has been considered as a potential target for development anticancer therapeutics. Here, we report novel mechanism by which the cyclopentenone prostaglandin, 15-deoxy-?12,14-prostaglandin J2 (15d-PGJ2) functions an allosteric inhibitor STAT3. 15d-PGJ2 inhibits phosphorylation, dimerization, nuclear translocation, transcriptional activity STAT3 in H-Ras-transformed human mammary epithelial cells (MCF10A-Ras) through Michael addition reaction at cysteine 259 Comparative studies with analogues reveal that both C12-C13 C9-C10 double bonds conjugated to carbonyl group ring are essential binding. Antiproliferative pro-apoptotic activities MCF10A-Ras attributable covalent modification on Cys259, mimic effects induced mutation this amino acid.
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ژورنال
عنوان ژورنال: FEBS Letters
سال: 2021
ISSN: ['0014-5793', '1873-3468']
DOI: https://doi.org/10.1002/1873-3468.14040