Histone Deacetylase 7 Promotes PML Sumoylation and Is Essential for PML Nuclear Body Formation

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.

SUPPLEMENTAL MATERIAL

Supplemental material for this article may be found at http://mcb.asm.org/ .

ACKNOWLEDGMENTS

We thank D. Samols and E. Stavnezer for their comments on the manuscript.

Kristopher J. Stanya and Erin Reineke are supported by T32 GM08056 and T32 CA059366-11, respectively. This project is supported by NIH/NIDDK R01 DK62985, by a grant from the American Cancer Society (RSG GMC-106736) to Hung-Yin Kao, and by the Confocal Microscopy Core Facility of the Comprehensive Cancer Center of Case Western Reserve University and University Hospitals of Cleveland (through NIH P30 CA43703-12). Hsiu-Ming Shih is supported by NSC (Taiwan) grant no. 96-2321-B-001-026.