Chapter title |
Assessment of HDACi-Induced Protein Cleavage by Caspases
|
---|---|
Chapter number | 2 |
Book title |
HDAC/HAT Function Assessment and Inhibitor Development
|
Published in |
Methods in molecular biology, January 2017
|
DOI | 10.1007/978-1-4939-6527-4_2 |
Pubmed ID | |
Book ISBNs |
978-1-4939-6525-0, 978-1-4939-6527-4
|
Authors |
Fabian Treude, Tobias Gladbach, Jacqueline Plaster, Jörg Hartkamp |
Abstract |
Aberrant histone deacetylase (HDAC) activity often correlates with neoplastic transformation and inhibition of HDACs by small molecules has emerged as a promising strategy to treat hematological malignancies in particular. Treatment with HDAC inhibitors (HDACis) often prompts tumor cells to undergo apoptosis, thereby causing a caspase-dependent cleavage of target proteins. An unexpectedly large number of proteins are in vivo caspase substrates and defining caspase-mediated substrate specificity is a major challenge. In this chapter we demonstrate that the hematopoietic transcription factor PU.1 becomes cleaved after treatment of acute myeloid leukemia (AML) cells with the HDACis LBH589 (panobinostat) or MS-275 (entinostat). To define caspase specificity for PU.1, an in vitro caspase assay including caspases 1-10 with in vitro-translated PU.1 is described in detail. |
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