MG132 targets proteasome to inhibit its activity, but it does not inhibit E3 ligase. Then why will MG132 will lead to accumulation of unubiquitylated protein level in a cell?
Dear Jen i-chen,
the proteasome doesn't only degrade substrate proteins but it also "recycles" the poly-ubiquitin chains that the substrate proteins were labeled with. This is done through disassembly of the ubiquitin chains by the proteasome-associated deubiquitylating enzymes. Disassembly of ubiquitin chains is also blocked when the catalytic activity of the proteasome is inhibited by MG132 and substrates can not be processed anymore. This very rapidly leads to a depletion of free monoubiquitin in the cells, so that there's not enough mono-ubiquitin present for the E3 ligases to attach them to the client proteins. Therefore, client proteins accumulate in a non-ubiquitinated state.
Hope this helps.
Best,
Katrin
It does not. MG132 inhibits proteasome-dependent degradation. Accumulation of Ub-conjugated complexes becomes easily detectable as they are not degraded in the presence of this protease inhibitor.
This explanation (from Katrin Bagola) seems very logical. I have considered this question for a while as well. Is there any reference for MG132 inhibition of the interaction between DUB and proteasome?
Does the accumulation of ubiquitin decrease after treatment with MG132? After treating cells with MG132 for 3 hours I observe a reduction in accumulated ubiquitin. Why does this happen?
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