Caspase-3 and Caspase-6 cleave STAT1 in leukemic cells

Signal Transducer and Activator of Transcription-1 (STAT1) is phosphorylated upon interferon (IFN) stimulation, which can restrict cell proliferation and survival. Nevertheless, in some cancers STAT1 can act in an anti-apoptotic manner. Moreover, certain malignancies are characterized by the overexp...

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Main Authors:	Licht, Verena, Noack, Katrin, Schlott, Bernhard, Förster, Martin, Schlenker, Yvonne, Licht, Andreas, Krämer, Oliver H., Heinzel, Thorsten
Format:	Online
Language:	English
Published:	Impact Journals LLC 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039164/

id	pubmed-4039164
recordtype	oai_dc
spelling	pubmed-40391642014-06-10 Caspase-3 and Caspase-6 cleave STAT1 in leukemic cells Licht, Verena Noack, Katrin Schlott, Bernhard Förster, Martin Schlenker, Yvonne Licht, Andreas Krämer, Oliver H. Heinzel, Thorsten Research Paper Signal Transducer and Activator of Transcription-1 (STAT1) is phosphorylated upon interferon (IFN) stimulation, which can restrict cell proliferation and survival. Nevertheless, in some cancers STAT1 can act in an anti-apoptotic manner. Moreover, certain malignancies are characterized by the overexpression and constitutive activation of STAT1. Here, we demonstrate that the treatment of transformed hematopoietic cells with epigenetic drugs belonging to the class of histone deacetylase inhibitors (HDACi) leads to the cleavage of STAT1 at multiple sites by caspase-3 and caspase-6. This process does not occur in solid tumor cells, normal hematopoietic cells, and leukemic cells that underwent granulocytic or monocytic differentiation. STAT1 cleavage was studied under cell free conditions with purified STAT1 and a set of candidate caspases as well as with mass spectrometry. These assays indicate that unmodified STAT1 is cleaved at multiple sites by caspase-3 and caspase-6. Our study shows that STAT1 is targeted by caspases in malignant undifferentiated hematopoietic cells. This observation may provide an explanation for the selective toxicity of HDACi against rapidly proliferating leukemic cells. Impact Journals LLC 2014-04-18 /pmc/articles/PMC4039164/ /pubmed/24810717 Text en Copyright: © 2014 Licht et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Licht, Verena Noack, Katrin Schlott, Bernhard Förster, Martin Schlenker, Yvonne Licht, Andreas Krämer, Oliver H. Heinzel, Thorsten
spellingShingle	Licht, Verena Noack, Katrin Schlott, Bernhard Förster, Martin Schlenker, Yvonne Licht, Andreas Krämer, Oliver H. Heinzel, Thorsten Caspase-3 and Caspase-6 cleave STAT1 in leukemic cells
author_facet	Licht, Verena Noack, Katrin Schlott, Bernhard Förster, Martin Schlenker, Yvonne Licht, Andreas Krämer, Oliver H. Heinzel, Thorsten
author_sort	Licht, Verena
title	Caspase-3 and Caspase-6 cleave STAT1 in leukemic cells
title_short	Caspase-3 and Caspase-6 cleave STAT1 in leukemic cells
title_full	Caspase-3 and Caspase-6 cleave STAT1 in leukemic cells
title_fullStr	Caspase-3 and Caspase-6 cleave STAT1 in leukemic cells
title_full_unstemmed	Caspase-3 and Caspase-6 cleave STAT1 in leukemic cells
title_sort	caspase-3 and caspase-6 cleave stat1 in leukemic cells
description	Signal Transducer and Activator of Transcription-1 (STAT1) is phosphorylated upon interferon (IFN) stimulation, which can restrict cell proliferation and survival. Nevertheless, in some cancers STAT1 can act in an anti-apoptotic manner. Moreover, certain malignancies are characterized by the overexpression and constitutive activation of STAT1. Here, we demonstrate that the treatment of transformed hematopoietic cells with epigenetic drugs belonging to the class of histone deacetylase inhibitors (HDACi) leads to the cleavage of STAT1 at multiple sites by caspase-3 and caspase-6. This process does not occur in solid tumor cells, normal hematopoietic cells, and leukemic cells that underwent granulocytic or monocytic differentiation. STAT1 cleavage was studied under cell free conditions with purified STAT1 and a set of candidate caspases as well as with mass spectrometry. These assays indicate that unmodified STAT1 is cleaved at multiple sites by caspase-3 and caspase-6. Our study shows that STAT1 is targeted by caspases in malignant undifferentiated hematopoietic cells. This observation may provide an explanation for the selective toxicity of HDACi against rapidly proliferating leukemic cells.
publisher	Impact Journals LLC
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039164/
_version_	1612094793269116928

Caspase-3 and Caspase-6 cleave STAT1 in leukemic cells

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