A Proteomic Approach Identifies Isoform-Specific and Nucleotide-Dependent RAS Interactions.

Active mutations in the RAS genes are found in ∼30% of human cancers. Although thought to have overlapping functions, RAS isoforms show preferential activation in human tumors, which prompted us to employ a comparative and quantitative proteomics approach to generate isoform-specific and nucleotide-dependent interactomes of the four RAS isoforms, KRAS4A, KRAS4B, HRAS, and NRAS. Many isoform-specific interacting proteins were identified, including HRAS-specific CARM1 and CHK1 and KRAS-specific PIP4K2C and IPO7.

Activity-Guided Design of HDAC11-Specific Inhibitors.

Mammalian histone deacetylases (HDACs) are a class of enzymes that play important roles in biological pathways. Existing HDAC inhibitors target multiple HDACs without much selectivity. Inhibitors that target one particular HDAC will be useful for investigating the biological functions of HDACs and for developing better therapeutics.

Comparative Nucleotide-Dependent Interactome Analysis Reveals Shared and Differential Properties of KRas4a and KRas4b.

The KRAS gene encodes two isoforms, KRas4a and KRas4b. Differences in the signaling functions of the two KRas proteins are poorly understood. Here we report the comparative and nucleotide-dependent interactomes of KRas4a and KRas4b.

HDAC8 Catalyzes the Hydrolysis of Long Chain Fatty Acyl Lysine.

The histone deacetylase (HDAC) family regulates many biological pathways through the deacetylation of lysine residues on histone and nonhistone proteins. Mammals have 18 HDACs that are classified into four classes. Class I, II, and IV are zinc-dependent, while class III is nicotinamide adenine dinucleotide (NAD)-dependent lysine deacetylase or sirtuins.