The metalloprotease ADAM10 (a disintegrin and metalloprotease 10) undergoes rapid, postlysis autocatalytic degradation

What is it about?

The metalloprotease ADAM10 is an enzyme with important functions, for example during embryonic development and in the brain, but is also linked to diseases, such as Alzheimer's disease and cancer. Yet, it has been challenging to study the molecular properties and functions of ADAM10, because only low levels of the active form of this enzyme were detected. This new study demonstrates that in commonly used experimental settings the active form of ADAM10 is rapidly degraded through an unusual mechanism. Exploiting this mechanism allows prevention of ADAM10 degradation and enables consistent detection of high levels of active ADAM10. This approach made it possible to answer several open questions in the research field and demonstrates that - in contrast to previous assumptions - ADAM10 undergoes efficient maturation in cells, yielding a relatively stable and long-lived mature and active form. This work is instrumental for future mechanistic, biochemical, functional, structural and therapeutic studies on ADAM10.

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