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    Protein degradation

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    In addition to protein phosphorylation and dephosphorylation, protein degradation also plays key role in regulating signal transduction pathways and cell proliferation. Please answer the following questions:

    (1). Please give one example to describe how protein degradation regulates signal transduction pathway;

    (2) Please give another example to describe how protein degradation affects cell proliferation.

    (3). Do you think targeting protein degradation process could be an effective cancer therapeutic strategy? If your answer is YES, please describe which protein involving protein degradation process could be a good drug target for cancer therapy and how to design the drug targeting it? If your answer is NO, please explain why.

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    1. Protease-activated receptors (or PARs) are receptors which become activated through the activity of a protease. These PARs are a series of four G protein-coupled receptors. Cleavage within the extracellular N-terminus region exposes a linked domain which binds to and activates the receptor. Such receptors are involved in numerous signalling pathways. Once cleaved, these receptors cannot be reused by the cell. As a result, to turn off the signal, they are internalized and degraded by the cell. For the cell to become sensitive to this type of activation again, it must synthesize new receptors or mobilize pre-existing ones.

    One example is the ...