how deubiquitinating enzymes(DUBs) affect overall Proteosomal activity in cells?
I not sure on the overall affect on cellular activity, but the proteosomal acitivity is dependent on the ubiquitination state (mono- poly - or muti-ubiquitination) of the target substrate. DUBS removes/modify the ubiquitination of the target substrate thereby altering the fate (trafficking) of the target substrate. Hope that help.
Like Kevin indicated, DUBs can counteract ubiquitinating machinery by cleaving ubiquitin adducts from proteins that have been targeted for degradation. Also, the proteasome itself has 3 resident DUBs: Rpn11, Uch37, and Usp14. Their activity is required so that substrates that have been polyubiquitinated and thus targeted for proteasomal degradation, can be deubiquitinated. This facilitates ATP-dependent unfolding of the substrate, and followed by opening of the gate, enabling its translocation into the core particle and its cleavage into small peptides.
Thanks Judith..Very insightful.....I am a bit naive in Proteosomal degradation pathway...but i find it very interesting.....I was wondering if proteosomal activity is enhanced in cells,does it mean the activity of DUBs are suppressed?
That could be one possibility, but its unlikely that all the DUBs are suppressed in a cell. Proteasome activity can increase due to a wide variety of factors such as stress response, etc.
While its true that "DUBs" in general will not be regulated in concert, as Judith mentioned,there are certain DUBs (USP14, UCH37, POH1 (Rpn11) that will directly affect proteasome by editing ubiquitin chains right at the proteasome. Its thought that if a substrate is relatively hypo-ubiquitinated that this activity might liberate the substrate before degradation.
The enzyme UCH-L1 is thought to be important in maintaining the levels of mono-ubiquitin in cells (neuronal, tumor) and in turn the level of mono-ubiquitin may impact proteasome activity if there is a relative deficiency of ubiquitin available for conjugation. Also, some DUBS are more promiscuous (e.g. USP2) such that over-expression may change the ubiquitination status of many substrates at once.
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