Post-translational modifications in drug resistance

Resistance to antitumor drugs, antimicrobial drugs, and antiviral drugs severely limits treatment effectiveness and cure rate of diseases. Protein post-translational modifications (PTMs) represented by glycosylation, ubiquitination, SUMOylation, acetylation, phosphorylation, palmitoylation, and lactylation are closely related to drug resistance. PTMs are typically achieved by adding sugar chains (glycosylation), small proteins (ubiquitination), lipids (palmitoylation), or functional groups (lactylation) to amino acid residues. These covalent additions are usually the results of signaling cascades and could be reversible, with the triggering mechanisms depending on the type of modifications. PTMs are involved in antitumor drug resistance, not only as inducers of drug resistance but also as targets for reversing drug resistance. Bacteria exhibit multiple PTMs-mediated antimicrobial drug resistance. PTMs allow viral proteins and host cell proteins to form complex interaction networks, inducing complex antiviral drug resistance. This review summarizes the important roles of PTMs in drug resistance, providing new ideas for exploring drug resistance mechanisms, developing new drug targets, and guiding treatment plans.