Version 1
: Received: 5 September 2024 / Approved: 6 September 2024 / Online: 6 September 2024 (12:10:59 CEST)
How to cite:
Asaad, L. A.; Pepperrell, B.; Furlong, F. Regulation of HDAC6 Catalytic Activity in Cancer: The Role of Post-translational Modifications and Protein-Protein Interactions. Preprints2024, 2024090519. https://doi.org/10.20944/preprints202409.0519.v1
Asaad, L. A.; Pepperrell, B.; Furlong, F. Regulation of HDAC6 Catalytic Activity in Cancer: The Role of Post-translational Modifications and Protein-Protein Interactions. Preprints 2024, 2024090519. https://doi.org/10.20944/preprints202409.0519.v1
Asaad, L. A.; Pepperrell, B.; Furlong, F. Regulation of HDAC6 Catalytic Activity in Cancer: The Role of Post-translational Modifications and Protein-Protein Interactions. Preprints2024, 2024090519. https://doi.org/10.20944/preprints202409.0519.v1
APA Style
Asaad, L. A., Pepperrell, B., & Furlong, F. (2024). Regulation of HDAC6 Catalytic Activity in Cancer: The Role of Post-translational Modifications and Protein-Protein Interactions. Preprints. https://doi.org/10.20944/preprints202409.0519.v1
Chicago/Turabian Style
Asaad, L. A., Benjamin Pepperrell and Fiona Furlong. 2024 "Regulation of HDAC6 Catalytic Activity in Cancer: The Role of Post-translational Modifications and Protein-Protein Interactions" Preprints. https://doi.org/10.20944/preprints202409.0519.v1
Abstract
Histone Deacetylase 6 (HDAC6) is a large multidomain protein that deacetylates lysine residues on cytoplasmic proteins, influencing a wide range of cellular processes. Both the catalytic and non-catalytic functions of HDAC6 are implicated in cancer development and progression. Over a decade of clinical trials with catalytic domain inhibitors, such as Ricolinostat (ACY1215), has shown that these drugs are well tolerated and can alleviate chemotherapy-induced peripheral neuropathies. However, their effectiveness in treating solid tumors remains uncertain due to the limited number of clinical trials and the small size of patient cohorts, leading to inconclusive results. HDAC6 activity is regulated by protein-protein interactions and post-translational modifications, which may allosterically influence its catalytic domains. Therefore, targeting HDAC6 in cancer therapy with small molecule inhibitors requires a more sophisticated understanding of its role within the tumor microenvironment, including whether its expression correlates with deacetylase activity. A comprehensive evaluation of both its enzymatic and non-enzymatic functions could be crucial in developing more effective strategies for targeting HDAC6 in cancer.
Keywords
HDAC6; Cancer; phosphorylation; acetylation; PPI
Subject
Medicine and Pharmacology, Oncology and Oncogenics
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
