Determination of IUP based on susceptibility for degradation by default.

Intrinsically unstructured proteins (IUPs) like the structured proteins are subjected to proteasomal degradation. However, unlike the structured ones, there is no crucial need of protein unfolding step to access the IUPs to the 20S catalytic subunit of the proteasome. This distinctive behavior set the stage for operational definition of the IUPs based on their susceptibility to the 20S degradation in a cell free system. Numerous studies revealed that this is the case in the cells as well, although no comprehensive analysis was performed to date. IUPs are degraded by the 20S proteasome subunit by default, without being polyubiquitinated or undergoing any other modifications. IUPs escape the process of degradation by default by a number of mechanisms, of which a more general one is interaction with a partner named nanny. Based on these attributes one can define IUP by conducting a set of cell free and cell culture experiments as outlined in this chapter.