2021-11-22

International Harmonization of Provisional Diagnostic Criteria for ERBB2-Amplified Metastatic Colorectal Cancer Allowing for Screening by Next-Generation Sequencing Panel

ERBB2 amplification (human epidermal growth factor receptor 2 positivity [HER2+]) in metastatic colorectal cancer (mCRC) has important therapeutic implications that necessitate the need for accurate diagnostics. The study purpose was to establish and validate harmonized diagnostic criteria for HER2+ mCRC among 3 groups (GI-SCREEN-Japan, NCTN-SWOG-USA, and Korea).
2021-11-22

Structure-based screening combined with computational and biochemical analyses identified the inhibitor targeting the binding of DNA Ligase 1 to UHRF1

The accumulation of epigenetic alterations is one of the major causes of tumorigenesis. Aberrant DNA methylation patterns cause genome instability and silencing of tumor suppressor genes in various types of tumors. Therefore, drugs that target DNA methylation-regulating factors have great potential for cancer therapy.
2021-11-19

Cryo-EM reveals Mechanistic Insights into Lipid-facilitated Polyamine Export by Human ATP13A2

The cytoplasmic polyamine maintains cellular homeostasis by chelating toxic metal cations, regulating transcriptional activity, and protecting DNA. ATP13A2 was identified as a lysosomal polyamine exporter responsible for polyamine release into the cytosol, and its dysfunction is associated with Alzheimer’s disease and other neural degradation diseases. ATP13A2 belongs to the P5 subfamily of the P-type ATPase family, but its mechanisms remain unknown.
2021-11-16

Structural basis of the regulation of the normal and oncogenic methylation of nucleosomal histone H3 Lys36 by NSD2

Dimethylated histone H3 Lys36 (H3K36me2) regulates gene expression, and aberrant H3K36me2 upregulation, resulting from either the overexpression or point mutation of the dimethyltransferase NSD2, is found in various cancers. Here we report the cryo-electron microscopy structure of NSD2 bound to the nucleosome.