ADAMTS-12: Functions and Challenges for a Complex Metalloprotease.

Nineteen members of the ADAMTS family of secreted zinc metalloproteinases are present in the human degradome. A wide range of different functions are being attributed to these enzymes and the number of their known substrates is considerably increasing in recent years. ADAMTSs can participate in processes such as fertility, inflammation, arthritis, neuronal and behavioral disorders, as well as cancer. Since its first annotation in 2001, ADAMTS-12 has been described to participate in different processes displayed by members of this family of proteinases. In this sense, ADAMTS-12 performs essential roles in modulation and recovery from inflammatory processes such as colitis, endotoxic sepsis and pancreatitis. ADAMTS-12 has also been involved in cancer development acting either as a tumor suppressor or as a pro-tumoral agent. Furthermore, participation of ADAMTS-12 in arthritis or in neuronal disorders has also been suggested through degradation of components of the extracellular matrix. In addition, ADAMTS-12 proteinase activity can also be modified by interaction with other proteins and thus, can be an alternative way of modulating ADAMTS-12 functions. In this review we revised the most relevant findings about ADAMTS-12 function on the 20th anniversary of its identification.