Charge‐mediated proteasome targeting

What is it about?

Ubiquitin-proteasome system (UPS) consisting of more than one thousand proteins maintains intracellular metabolism of half of cell proteome and is critical for cell functioning. Absolute majority of proteins are recognized by proteolytic machine (proteasome) only as covalent conjugate with ubiquitin (Ub) molecules, which are attached by ubiquitination system (cascade of hundreds of Ub-ligases). As an exception, proteasome may recognize and degrade non-ubiquitinated proteins, containing distinct amino acid composition that is directly engaged by proteasome. Here we show that basic charge may be novel type of direct proteasome signals (DPS), that target proteins to proteasome without Ub. Universality of discovered principle is demonstrated by conjugation of proteins with chemical compounds with basic charge that convert them into the Ub-independent proteasome substrates.

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