degron

A degron is a sequence or structural feature within a protein that signals its degradation by the ubiquitin-proteasome system. Degrons are recognized by E3 ubiquitin ligases, which catalyze the attachment of ubiquitin chains to the substrate and promote its destruction by the proteasome. Degrons can be located at the N-terminus, the C-terminus, or within the protein core, and may be constitutively present or exposed only under certain conditions, such as misfolding or post-translational modification.

N-degrons and the N-end rule pathway. In this pathway, the identity of the N-terminal residue influences protein stability. Some N-terminal residues act as primary destabilizing signals and recruit specific N-recognins; other residues require enzymatic processing, such as deamidation or arginylation, to become destabilizing. This leads to ubiquitination and proteasomal degradation. N-recognins include members of the UBR family in mammals and yeast.

C-degrons and APC/C. Degrons at the C-terminus or motifs that recruit particular E3 ligases contribute to regulated degradation. In cell-cycle control, the APC/C ubiquitin ligase recognizes D-box and KEN-box degrons in substrates, triggering ubiquitination and timely degradation during mitosis and exit from mitosis.

Phospho-degrons and other signals. Phosphorylation can generate degrons that are recognized by SCF-type E3 ligases, for example beta-TrCP recognizing phosphorylated DSGxxS motifs. Other degrons include PEST sequences and various internal degrons that become exposed upon misfolding or stress.

Significance. Degrons regulate protein levels and signaling pathways; mutations that disrupt degrons stabilize proteins and can contribute to disease, while engineered degrons are used to control protein half-life in research and biotechnology. The degron concept, introduced in N-end rule studies by Varshavsky and colleagues, highlights how sequence and structure determine protein fate.