The Ubiquitin Proteasome System

Question 1

What is the function of the ubiquitin proteasome pathway?

Answer 1

It functions to degrade proteins from the cytoplasm, nucleus and endoplasmic reticulum (ER).

Question 2

What is molecule proteins are tagged with for degradation?

Answer 2

They are tagged with ubiquitin at a lysine residue in their structure.

Question 3

How are proteins tagged for degradation?

Answer 3

1) A E1 enzyme adenylylates a ubiquitin molecule.
2) The adenylyated ubiquitin is then transferred to a E2 enzyme.
3) An E3 enzyme then recognises the protein to be degraded and catalyses the transfer of ubiquitin from E2 the target protein.

Question 4

How is protein degradation responsive to nutrition?

Answer 4

Several subunits of the proteasome are glycosylated with GlcNAc when extracellular glucose is high. This leads to decreased intracellular proteolysis. (Vice versa)

Question 5

What are the two main types of Ubiquitin Ligases?

Answer 5

HECT, RING fingers.

Question 6

What causes Liddle’s Disease?

Answer 6

Mutations in the Nedd4. These mutations cause accumulation of epithelial sodium channels at the cell surface, and thus hypertension.

Question 7

What is Nedd4?

Answer 7

A ubiquitin protein part of of the sub-family of HECT E3s that binds to the subunits of epithelial sodium channels.

Question 8

What is the function of the epithelial sodium channels (ENaC)?

Answer 8

They function to control salt and fluid resorption in the kidneys.