Very recently, the wild type α-lytic protease was shown to cleave small ubiquitin-like modifier (SUMO) modified proteins to form a GG-K remnant, thus providing a new strategy for mapping of SUMO-modified proteins without the need for introduction of mutations.
K48-linked polyubiquitination is well recognized as a targeting signal that allows modified proteins to undergo 26S proteasome-dependent degradation.
As demonstrated by current protocols, their unique mechanisms can be coupled with synthetic inhibitors or genetically modified proteins to create effective first-line therapies.
Recent advances that enable large sets of modified proteins to be identified, combined with global analyses of gene expression, have provided an opportunity for a systems-based approach to study electrophile stress at the cellular level.
The scheme indicates also some more hypothetical links to observations in mammalian cells, for instance as to the post-prenylation reactions and the transport of covalently modified proteins to their intracellular destination.
In principle, the introduction of multiple nucleobase amino acids into the nucleic acid binding domain of a protein should enable these modified proteins to interact with their nucleic acid substrates using Watson-Crick and other base pairing interactions.
