Histone deacetylase 7 promotes PML sumoylation and is essential for PML nuclear body formation.
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.
Gao
Chengzhuo
C
Department of Biochemistry, School of Medicine, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106, USA.
Ho
Chun-Chen
CC
Reineke
Erin
E
Lam
Minh
M
Cheng
Xiwen
X
Stanya
Kristopher J
KJ
Liu
Yu
Y
Chakraborty
Sharmistha
S
Shih
Hsiu-Ming
HM
Kao
Hung-Ying
HY
D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006367:HeLa Cells; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D045586:Intranuclear Inclusion Bodies / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D000071156:Promyelocytic Leukemia Protein; D011499:Protein Processing, Post-Translational; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D014471:Umbilical Veins / Q000166:cytology
D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; C543273:HDAC7 protein, human; D006655:Histone Deacetylases