EGFR phosphorylates HDAC1 to regulate its expression and anti-apoptotic function
Autor: | Nuwan P. N. Acharige, Mary Kay H. Pflum, Hongbo Ling, Edward Seto, Irene Santos-Barriopedro, Sonali Bahl |
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Rok vydání: | 2020 |
Předmět: |
Cancer Research
animal structures DNA repair Immunology Apoptosis Histone Deacetylase 1 Transfection Article Cellular and Molecular Neuroscience chemistry.chemical_compound Humans Phosphorylation QH573-671 biology Tyrosine phosphorylation Cell Biology HDAC1 Cell biology ErbB Receptors enzymes and coenzymes (carbohydrates) Histone chemistry embryonic structures biology.protein Histone deacetylase biological phenomena cell phenomena and immunity Signal transduction Cytology Corepressor Chemical modification |
Zdroj: | Cell Death & Disease Cell Death and Disease, Vol 12, Iss 5, Pp 1-17 (2021) |
ISSN: | 2041-4889 |
Popis: | HDAC1 is the prototypical human histone deacetylase (HDAC) enzyme responsible for catalyzing the removal of acetyl group from lysine residues on many substrate proteins. By deacetylating histones and non-histone proteins, HDAC1 has a profound effect on the regulation of gene transcription and many processes related to cell growth and cell death, including cell cycle progression, DNA repair, and apoptosis. Early studies reveal that, like most eukaryotic proteins, the functions and activities of HDAC1 are regulated by post-translational modifications. For example, serine phosphorylation of HDAC1 by protein kinase CK2 promotes HDAC1 deacetylase enzymatic activity and alters its interactions with proteins in corepressor complexes. Here, we describe an alternative signaling pathway by which HDAC1 activities are regulated. Specifically, we discover that EGFR activity promotes the tyrosine phosphorylation of HDAC1, which is necessary for its protein stability. A key EGFR phosphorylation site on HDAC1, Tyr72, mediates HDAC1’s anti-apoptotic function. Given that HDAC1 overexpression and EGFR activity are strongly related with tumor progression and cancer cell survival, HDAC1 tyrosine phosphorylation may present a possible target to manipulate HDAC1 protein levels in future potential cancer treatment strategies. |
Databáze: | OpenAIRE |
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