The promyelocytic leukemia protein PML acts as a tumor suppressor by forming transcription-regulatory complexes with a variety of repressor proteins. In the present study, we found that endogenous PML suppresses interleukin (IL)-6-induced gene expression as well as phosphorylation and transcriptional activation of STAT3 in hepatoma cells. We also found that PML-mediated suppression of IL-6-induced STAT3 activation by disrupting interactions between STAT3 and HDAC3. These results indicate that PML modulates IL-6-induced STAT3 activation and hepatoma cell growth by interacting with HDAC3.
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http://dx.doi.org/10.1016/j.bbrc.2015.04.040 | DOI Listing |
Exp Mol Pathol
December 2024
Rheumatology Unit, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), University of Bari, Bari, Italy.
Interleukin-6 (IL-6) is a relevant cytokine in rheumatoid arthritis (RA) pathogenesis, potentially activating Janus kinases (JAK)-1, -2, and tyrosine kinase 2 (TYK2), and thus, three signal transducer and activator of transcription (STAT)-1, -3 or - 5 pathways. This pilot study aims to explore differences in phosphorylated (p)STAT3 levels among patients with RA, those not classified as RA (nRA), and healthy donors (HD), providing some clues on the relative contribution of each JAK protein to the downstream of the IL-6-induced STAT3 pathway. Clinical data and blood samples from 80 subjects (41 RA, 14 nRA, and 25 HD) were collected.
View Article and Find Full Text PDFMol Med Rep
February 2025
Department of Gastroenterology, Xiangtan Central Hospital, Xiangtan, Hunan 411100, P.R. China.
Clin Immunol
November 2024
Division of Immunology, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA. Electronic address:
Bioorg Med Chem Lett
December 2024
School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan. Electronic address:
The inhibitory activities of phaeosphaeride A (PPA), phaeosphaeride B, and four synthetic derivatives against phosphorylation of signal transducer and activator of transcription 3 (STAT3) and cell proliferation in cervical (HeLa) and breast (MDA-MB-231) cancer cells were evaluated. PPA inhibited IL-6-induced STAT3 phosphorylation and cell proliferation at similar concentrations. The structure-activity relationship studies revealed that the enantiomer of PPA was the most potent of the evaluated phaeosphaerides in both inhibiting STAT3 phosphorylation and cell growth.
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