Histone deacetylases 1/2 as critical factors in protein synthesis and tumorigenesis
Ting Lu, Xiang Xu
Histone deacetylases (HDACs) co-repress transcription by deacetylating histone tails. HDAC1 and HDAC2, as highly related proteins, have crucial functions in physiology and development. HDAC1 has premier role in mediation of cyclin-dependent kinase inhibitor p21, and HDAC1-knockout mice are embryonic lethal. Silencing of HDAC1 leads to disturb of the cell cycle with mitotic cell loss. HDAC2 also deacetylases non-histone proteins. Cap binding protein Eukaryotic translation initiation factor 4E (eIF4E) binds the 5’ cap structure of messenger RNAs (mRNAs). The sumoylation of eIF4E is promoted by HDAC2, the sumoylation of eIF4E is independent from its deacetylating activity. The sumoylation of eIF4E promotes the formation of eIF4F translation complex that induces translation of a series of important proteins that are essential for cell proliferation and preventing cell apoptosis. Disruption of eIF4E sumoylation leads to abrogation of mRNA translation of the series of proteins. These data implies it is meaningful to study sumoylation as a novel regulatory mechanism for protein synthesis and eIF4E as a critical factor for potential oncological study. HDAC2 is overexpressed in a number of tumor types, implying its role in tumorigenesis. As understood the tumor suppressor factor p53 in human tumors is often silenced, p53 gene is often mutated. The molecular reason for p53 inactivation remains to be defined. Remarkably, recent findings show the overexpression of HDAC2 in tumor cells has links to the inactivation of p53. Here we show in solid and hematopoeotic cancers overexpressed HDAC2 has links with p53 silence in vivo and in vitro. Further study of the relationship of p53 and HDAC2 can help bring new ideas to cancer therapy.