mg-132

Overview

MG-132 (Z-Leu-Leu-Leu-al) is a reversible, cell-permeable proteasome inhibitor widely used as a tool compound to block ubiquitin-mediated proteasomal degradation. It is not approved for clinical use; the clinically approved proteasome inhibitor bortezomib shares the same mechanistic target (26S proteasome) but uses a different chemical scaffold. MG-132 is routinely used in biochemistry experiments to establish that a protein’s stability is controlled by the ubiquitin-proteasome system (UPS).

Evidence in the corpus

• MG-132 treatment rescued TRMT10A protein levels in 22Rv1 mCRPC cells after USP10 knockdown or spautin-1 (USP10 inhibitor) treatment, confirming that USP10 stabilizes TRMT10A by preventing its proteasomal degradation; without USP10 activity, TRMT10A is poly-ubiquitinated and degraded via the 26S proteasome PMID:28068672.

Resistance mechanisms

• Proteasomal degradation of TRMT10A (blocked by MG-132) is the primary mechanism by which USP10 inhibition (spautin-1) induces BRCAness in BRCA1/2-wild-type mCRPC; this places proteasome activity as a prerequisite for the spautin-1 + olaparib combination strategy PMID:28068672.

Cancer types (linked)

• PRAD — MG-132 used in mechanistic UPS experiments in mCRPC cell lines.

Sources

• PMID:28068672 — Yang et al., TRMT10A/USP10 axis in mCRPC; MG-132 used to confirm proteasome-dependent TRMT10A degradation.

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