Chien Lab Finds Protease Adaptors Regulate Own Destruction

Peter Chien
Peter Chien
Kamal Joshi
Kamal Joshi

For cells of all sorts, getting rid of proteins when they are no longer needed is essential to proper functioning, explains Peter Chien, biochemistry and molecular biology.

Biochemists have long known that many key cell processes depend on a highly regulated cleanup system in which specialized proteins called proteases degrade damaged or no-longer-needed proteins. The proteases must specifically destroy their targets without damaging other proteins, and for years the Chien lab has been studying and revealing the details of how this orderly destruction works.

In bacteria, Chien and colleagues had earlier discovered that proteins called adaptors deliver substrates – molecules upon which energy-dependent proteases act. These adaptors often work like tethers to hold their cargo close to the proteases so that they can be handed off efficiently, he says.

In a recent paper in the Journal of Biological Chemistry, Chien and Kamal Joshi, a doctoral candidate in the molecular and cellular biology graduate program, show that adaptor degradation is highly regulated in a specific, substrate-sensitive way.

The team set out to find out why the adaptors themselves were not degraded during this process. They found that adaptors could be degraded by proteases, but only when the adaptors weren’t already busy delivering substrates. If there was a substrate bound to the adaptors, the adaptors were protected from degradation. Hence their latest research article is titled “Cargo engagement protects protease adaptors from degradation in a substrate-specific manner.”

Chien notes, “Interestingly, when the adaptors had done their job and delivered all their substrates, the proteases would then degrade the adaptors.”

He adds that this type of self-limiting activity could be useful for the cell to make sure that substrates are only degraded when they really need to be. Because protease activity is crucial to virulence in bacterial pathogens, understanding how these adaptors are controlled could be used in developing new classes of antibiotics. 

Work in his lab is sponsored by the NIH National Institute of General Medical Sciences. The Chien lab is a member of the Models to Medicine Center in the Institute of Applied Life Sciences.

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