SIRT1 and p300/CBP, which are considered to be essential histone deacetylases and acetyltransferases, are also considered to be relative to tumorigenesis because they modulate the expression of several tumor suppressor genes. Therefore, this study investigated the expression of SIRT1 and p300/CBP in gastroesophageal junction (GEJ) cancer and their correlation with E-cadherin and MLH1 in order to explore the clinicopathological significance of SIRT1 and p300/CBP expression and their possible effects involving E-cadherin and MLH1 expression. Tissue microarray technique and immunohistochemical stains were applied to evaluate the SIRT1, p300/CBP, E-cadherin, and MLH1 expression in 176 GEJ cancer tissues and 32 normal GEJ region tissues. The results showed that the over-expression of SIRT1 was associated with a higher number of metastasis lymph nodes, more advanced staging, and shorter mean survival time. SIRT1 and p300/CBP were negatively and positively correlated with the expression of E-cadherin and MLH1, respectively, in the cancer cases. These results indicated a possible effect of SIRT1 and p300/CBP involved in regulating the expression of E-cadherin and MLH1, thus participating in the tumor progression of GEJ cancer.
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http://dx.doi.org/10.1016/j.prp.2013.03.012 | DOI Listing |
iScience
February 2024
Institute of Biochemistry and Biophysics, Centre for Molecular Biomedicine (CMB), Friedrich Schiller University, Hans-Knoell-Strasse 2, 07745 Jena, Germany.
Glucocorticoid (GC) signaling is essential for mounting a stress response, however, chronic stress or prolonged GC therapy downregulates the GC receptor (GR), leading to GC resistance. Regulatory mechanisms that refine this equilibrium are not well understood. Here, we identify seven lysine acetylation sites in the amino terminal domain of GR, with lysine 154 (Lys) in the AF-1 region being the dominant acetyl-acceptor.
View Article and Find Full Text PDFPharmaceuticals (Basel)
January 2023
Department of Nucleic Acid Biochemistry, Medical University of Lodz, 251 Pomorska Str., 92-213 Lodz, Poland.
Accumulating evidence (mainly from experimental research) suggests that metformin possesses anticancer properties through the induction of apoptosis and inhibition of the growth and proliferation of cancer cells. However, its effect on the enzymes responsible for histone acetylation status, which plays a key role in carcinogenesis, remains unclear. Therefore, the aim of our study was to evaluate the impact of metformin on histone acetyltransferases (HATs) (i.
View Article and Find Full Text PDFAging Cell
August 2022
Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
The transcription factor p300 is reportedly involved in age-associated human diseases, including intervertebral disc degeneration (IDD). In this study, we investigate the potential role and pathophysiological mechanism of p300 in IDD. Clinical tissue samples were collected from patients with lumbar disc herniation (LDH), in which the expression of p300, forkhead box O3 (FOXO3), and sirtuin 1 (Sirt1) was determined.
View Article and Find Full Text PDFCell Rep
January 2022
Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. Electronic address:
Aberrant BRAF activation, including the BRAF mutation, is frequently observed in human cancers. However, it remains largely elusive whether other types of post-translational modification(s) in addition to phosphorylation and ubiquitination-dependent regulation also modulate BRAF kinase activity. Here, we report that the acetyltransferase p300 activates the BRAF kinase by promoting BRAF K601 acetylation, a process that is antagonized by the deacetylase SIRT1.
View Article and Find Full Text PDFJ Genet Genomics
July 2021
Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. Electronic address:
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