The stem cell-supporting small molecule UM171 triggers Cul3-KBTBD4-mediated degradation of ELM2 domain-harboring proteins.

ABSTRACT: To chemically modulate the ubiquitin-proteasome system for the degradation of specific target proteins is currently emerging as an alternative therapeutic modality. Earlier, we discovered such properties of the stem cell-supporting small molecule UM171 and identified that members of the CoREST complex (RCOR1 and LSD1) are targeted for degradation. UM171 supports the in vitro propagation of hematopoietic stem cells by transiently perturbing the differentiation-promoting effects of CoREST. Here, we employed global proteomics to map the UM171-targeted proteome and identified the additional target proteins, namely RCOR3, RREB1, ZNF217, and MIER2. Further, we discovered that critical elements recognized by Cul3^KBTBD4 ligase in the presence of UM171 are located within the EGL-27 and M

SUBMITTER: Zemaitis K 

PROVIDER: S-EPMC10164905 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature