Proteins carry out their functions by interacting with other proteins and small molecules, forming a complex interaction network. In this review, we briefly introduce classical graph theory based protein-protein interaction networks. We also describe the commonly used experimental methods to construct these networks, and the insights that can be gained from these networks. We then discuss the recent transition from graph theory based networks to structure based protein-protein interaction networks and the advantages of the latter over the former, using two networks as examples. We further discuss the usefulness of structure based protein-protein interaction networks for drug discovery, with a special emphasis on drug repositioning.
Transposable elements(TEs)have been shown to have important gene regulatory functions and their alteration could lead to disease phenotypes.Acute myeloid leukemia(AML)develops as a consequence of a series of genetic changes in hematopoietic precursor cells,including mutations in epigenetic factors.Here,we set out to study the gene regulatory role of TEs in AML.We first explored the epigenetic landscape of TEs in AML patients using ATAC-seq data.We show that a large number of TEs in general,and more specifically mammalian-wide interspersed repeats(MIRs),are more enriched in AML cells than in normal blood cells.We obtained a similar finding when analyzing histone modification data in AML patients.Gene Ontology enrichment analysis showed that genes near MIRs in open chromatin regions are involved in leukemogenesis.To functionally validate their regulatory role,we selected 19 MIR regions in AML cells,and tested them for enhancer activity in an AML cell line(Kasumi-1)and a chronic myeloid leukemia(CML)cell line(K562);the results revealed several MIRs to be functional enhancers.Taken together,our results suggest that TEs are potentially involved in myeloid leukemogenesis and highlight these sequences as potential candidates harboring AML-associated variation.
HDAC6 is involved in several biological processes related to aging-associated diseases.However,it was unknown whether HDAC6 could directly regulate lifespan and healthspan.We found that HDAC6 knockdown induced transcriptome changes to attenuate the aging changes in the Drosophila head,particularly on the inflammation and innate immunity-related genes.Whole-body knockdown of HDAC6 extended lifespan in the fly,furthermore brain-specific knockdown of HDAC6 extended both lifespan and healthspan in the fly.Our results established HDAC6 as a lifespan regulator and provided a potential anti-aging target.
