FBXW7 E3 ubiquitin ligase:degrading,not degrading,or being degraded

It is well-established that FBXW7 acts as a tumor suppressor by promoting the polyubiquitylation via the K48 linkage of a broad range of oncoproteins for proteasome degradation.We and the others found that FBXW7 also recognizes noncanonical substrates,such as XRCC4 or y-catenin for polyubiquitylation via the K63 linkage,not for degradation,but for functional modulation.Most recently,we found that FBXW7 binds to a pseudo-substrate LSD1,not for degradation,rather being self-degraded.Thus,FBXW7 has three modes of action in a manner dependent of substrates,leading to different biological consequences.