HDAC2 promotes eIF4E sumoylation and activates mRNA translation gene specifically.
Histone deacetylases (HDACs) are best known as transcription corepressors through deacetylating histone tails. Here we show that HDAC2 is also involved in cap-dependent mRNA translation by promoting sumoylation of eukaryotic translation initiation factor 4E (eIF4E), which is independent of its deacetylase activity. By stimulating eIF4E sumoylation, HDAC2 induces the formation of the active eukaryotic initiation factor 4F (eIF4F) complex and induces the protein synthesis of a subset of eIF4E-responsive genes that are essential for cell proliferation and preventing apoptosis. These data demonstrate that HDAC2 has an unexpected sumoylation-promoting activity and regulates cap-dependent mRNA translation.
Xu
Xiang
X
Department of Pharmacology and Chemical Biology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
Vatsyayan
Jaya
J
Gao
Chenxi
C
Bakkenist
Christopher J
CJ
Hu
Jing
J
D017209:Apoptosis; D049109:Cell Proliferation; D003593:Cytoplasm / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D039561:Eukaryotic Initiation Factor-4E / Q000737:chemistry*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D056464:Histone Deacetylase 2 / Q000378:metabolism*; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D025842:SUMO-1 Protein / Q000378:metabolism*
D018076:DNA, Complementary; D039561:Eukaryotic Initiation Factor-4E; D012333:RNA, Messenger; D025842:SUMO-1 Protein; C495501:SUMO1 protein, human; D008156:Luciferases; C533423:HDAC2 protein, human; D056464:Histone Deacetylase 2