Abstract
Promyelocytic leukemia protein (PML) sumoylation has been proposed to control the formation of PML nuclear bodies (NBs) and is crucial for PML-dependent cellular processes, including apoptosis and transcriptional regulation. However, the regulatory mechanisms of PML sumoylation and its specific roles in the formation of PML NBs remain largely unknown. Here, we show that histone deacetylase 7 (HDAC7) knockdown reduces the size and the number of the PML NBs in human umbilical vein endothelial cells (HUVECs). HDAC7 coexpression stimulates PML sumoylation independent of its HDAC activity. Furthermore, HDAC7 associates with the E2 SUMO ligase, Ubc9, and stimulates PML sumoylation in vitro, suggesting that it possesses a SUMO E3 ligase-like activity to promote PML sumoylation. Importantly, HDAC7 knockdown inhibits tumor necrosis factor alpha-induced PML sumoylation and the formation of PML NBs in HUVECs. These results demonstrate a novel function of HDAC7 and provide a regulatory mechanism of PML sumoylation.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Line
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Cell Nucleus / metabolism
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Endothelial Cells / cytology
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Endothelial Cells / metabolism
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HeLa Cells
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Histone Deacetylases / genetics
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Histone Deacetylases / metabolism*
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Humans
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Intranuclear Inclusion Bodies / metabolism*
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Promyelocytic Leukemia Protein
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Protein Processing, Post-Translational*
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RNA, Small Interfering / genetics
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RNA, Small Interfering / metabolism
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Small Ubiquitin-Related Modifier Proteins / metabolism*
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Tumor Necrosis Factor-alpha / metabolism
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / metabolism*
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Umbilical Veins / cytology
Substances
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Nuclear Proteins
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Promyelocytic Leukemia Protein
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RNA, Small Interfering
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Recombinant Fusion Proteins
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Small Ubiquitin-Related Modifier Proteins
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Transcription Factors
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Tumor Necrosis Factor-alpha
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Tumor Suppressor Proteins
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PML protein, human
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HDAC7 protein, human
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Histone Deacetylases