Unlocking LAG3: Ubiquitin's unexpected role

Cell. 2025 May 1;188(9):2307-2309. doi: 10.1016/j.cell.2025.03.030.

Abstract

The inhibitory receptor LAG3 is the target of the FDA-approved mAb relatlimab, but its mechanism of signaling is not well understood. In this issue of Cell, Jiang et al. demonstrate that ubiquitination of its cytoplasmic domain is essential for the inhibitory function of LAG3. Co-expression of LAG3 and the CBL E3 ligases represents a biomarker of clinical response to LAG3 inhibition in human melanoma.

Publication types

  • Comment

MeSH terms

  • Antibodies, Monoclonal / therapeutic use
  • Humans
  • Lymphocyte Activation Gene 3 Protein
  • Melanoma / drug therapy
  • Melanoma / metabolism
  • Proto-Oncogene Proteins c-cbl / metabolism
  • Signal Transduction
  • Ubiquitin* / metabolism
  • Ubiquitination

Substances

  • Ubiquitin
  • Lymphocyte Activation Gene 3 Protein
  • Lag3 protein, human
  • Antibodies, Monoclonal
  • Proto-Oncogene Proteins c-cbl