20S proteasome is a proteolytic complex committed to degrade unfolded proteins

The Ubiquitin-Proteasome System: The Cell's Natural Destroyer.

Identification of a Ubiquitin-Independent Degron by a Reporter Assay.

Experimental strategies to identify UID degrons that mediate degradation by the catalytic 20S proteasome particle are described and an integrated workflow-spanning degron mapping to functional validation-provides a generalizable framework for uncovering ubiquitin-independent degrons.

Dissecting PROTAB-mediated degradation of cell surface proteins.

It is shown that PROTAB induces rapid ternary complex formation, followed by receptor internalization and degradation, resulting in ~ 85% target depletion within 24 h, and mechanistically, ubiquitination enhances but is not strictly required for internalization, and degradation proceeds predominantly through the lysoso...

Midnolin-directed protein degradation beyond ubiquitin.

This review compares midnolin-directed degradation with proteolysis-targeting chimeras and molecular glue degraders and identifies the design, delivery, and safety principles that will determine whether it becomes a useful ubiquitin-independent complement to existing degraders.

Trans-branching of polyubiquitin chains orchestrates the DNA replication stress response

Polyubiquitin chain geometry dictates functional consequences of ubiquitylation (1, 2). Although branched polyubiquitin chains are abundant in cells, little is known about their functions (3–5). Here we show that branching on the DNA replication factor PCNA, mediated by the ubiquitin-conjugating enzyme UBE2K and involv...

Activation and inactivation pathways of a p53-like transcription factor govern lipid homeostasis in yeast

Membrane fluidity depends on unsaturated acyl chains that are generated in Saccharomyces cerevisiae by the desaturase Ole1, whose expression is primarily under the control of the transcription factor Mga2. Here, we show that the endoplasmic reticulum-anchored Mga2 precursor is ubiquitinated by the E3 ligase Rsp5 and th...