PROTACs achieve degradation through "hijacking" the cell's ubiquitin–proteasome system (UPS) by bringing together the target protein and an E3 ligase. 
First, the E1 activates and conjugates the ubiquitin to the E2. The E2 then forms a complex with the E3 ligase. The E3 ligase targets proteins and covalently attaches the ubiquitin to the protein of interest. Eventually, after a ubiquitin chain is formed, the protein is recognized and degraded by the 26S proteasome. PROTACs take advantage of this cellular system by putting the protein of interest in close proximity to the E3 ligase to catalyze degradation.
Unlike traditional inhibitors, PROTACs have a catalytic mechanism, with the PROTAC itself being recycled after the target protein is degraded.