Differential substrate degradation by super-degron: EGFP in wild-type mouse cells, PD-1 requires CRBN humanization.

ABSTRACT: Protein knockdown using a zinc finger degron tag and thalidomide analogs was previously considered ineffective in mouse cells. However, using EGFP as an indicator, we found that a super-degron tag (SD) enables degradation in mouse cells when combined with iberdomide or mezigdomide. While SD-tagged EGFP was degraded in wild-type mouse cells, SD-tagged PD-1 required human-type CEREBLON (CRBN^I391V) for degradation. In mice with CRBN^I391V, endogenous PD-1 tagged with SD was efficiently degraded in T cells both in vitro and in vivo. Compared with anti-PD-1 antibody treatment, the degradation of PD-1 led to more rapid activation of CD8⁺ T cells. Moreover, pomalidomide that crosses the brain-blood barrier reduced PD-1 expression in the brain. These r

SUBMITTER: Naruse C 

PROVIDER: S-EPMC12274739 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature