Fig. 4
Schematic illustration of the degradation of modified proteins via the UPP and lysosomal pathways. The native protein, denatured by heat or H2O2, is degraded through the UPP pathway. The HNE-modified protein is degraded through the lysosomal pathway. In the UPP pathway, the ubiquitin ligase (E3) interacts with both the denatured protein and the conjugated enzyme. This process, known as protein ubiquitination modification, enables the lysine residue to interact with the ubiquitin chain (Ub). This protein ubiquitination modification produces a polyubiquitinated protein. E3 transfers the polyubiquitinated protein to the 26S proteasome. Ultimately, the polyubiquitinated protein is conjugated with the 19S proteasome (receptor) and degraded by the 20S proteasome, which contains the cleavage sites at the β subunits [159]. In the lysosomal pathway, E3 interacts with the HNE-modified protein and catalyses the transfer of Ub to an amino acid group of the modified protein. This process causes an isopeptide bond between Ub and lysine through mono-ubiquitylation. The monoubiquitinated protein is then degraded by lysosome [160]. The nature and structure of polyubiquitinated and mono-ubiquitinated proteins are listed in Table 1