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Updated: May 9, 2025

In Vitro Analysis of E3 Ubiquitin Ligase Function
Published on: May 14, 2021
Unlocking LAG3: Ubiquitin's unexpected role
Ye Zhao1, Kai W Wucherpfennig2
1Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
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.
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.
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