STAT3 Post-Translational Modifications Drive Cellular Signaling Pathways in Prostate Cancer Cells.
Rossana Cocchiola,Elisabetta Rubini,Fabio Altieri,Silvia Chichiarelli,Giuliano Paglia,Donatella Romaniello,Stefania Carissimi,Alessandra Giorgi,Flavia Giamogante,Alberto Macone,Giacomo Perugia,Aymone Gurtner,Margherita Eufemi +12 more
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TL;DR: Assessment of the correspondence between the stimulus-specificity of STAT3 PTMs and definite STAT3-mediated transcriptional programs, in order to identify new suitable pharmacological targets for PCa treatment, highlighted the role ofSTAT3 and its PTMs as drivers in the progression of PCa.
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Abstract: STAT3 is an oncoprotein overexpressed in different types of tumors, including prostate cancer (PCa), and its activity is modulated by a variety of post-translational modifications (PTMs). Prostate cancer represents the most common cancer diagnosed in men, and each phase of tumor progression displays specific cellular conditions: inflammation is predominant in tumor’s early stage, whereas oxidative stress is typical of clinically advanced PCa. The aim of this research is to assess the correspondence between the stimulus-specificity of STAT3 PTMs and definite STAT3-mediated transcriptional programs, in order to identify new suitable pharmacological targets for PCa treatment. Experiments were performed on less-aggressive LNCaP and more aggressive DU-145 cell lines, simulating inflammatory and oxidative-stress conditions. Cellular studies confirmed pY705-STAT3 as common denominator of all STAT3-mediated signaling. In addition, acK685-STAT3 was found in response to IL-6, whereas glutC328/542-STAT3 and pS727-STAT3 occurred upon tert-butyl hydroperoxyde (tBHP) treatment. Obtained results also provided evidence of an interplay between STAT3 PTMs and specific protein interactors such as P300 and APE1/Ref-1. In accordance with these outcomes, mRNA levels of STAT3-target genes seemed to follow the differing STAT3 PTMs. These results highlighted the role of STAT3 and its PTMs as drivers in the progression of PCa.
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The Roles of Post-Translational Modifications in STAT3 Biological Activities and Functions
TL;DR: In this paper, the authors describe the studies performed on the main modifications affecting the activity of STAT3: phosphorylation of tyrosine 705 and serine 727; acetylation of lysine 49, 87, 601, 615, 631, 685, 707, and 709; and methylation of Lysine 49.
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Post-Translational Modifications That Drive Prostate Cancer Progression
Ivana Samaržija
- 09 Feb 2021
TL;DR: A comprehensive list of proteome-wide and single protein post-translational modifications and their involvement in phenotypic outcomes is presented in this paper, where the data on phosphorylation, glycosylation, ubiquitination, SUMOylation and lipidation in prostate cancer and the enzymes involved are collected.
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