Structural Elucidation and Covalent Modulation of the Autorepressed Orphan Nuclear Receptor NR2F6.

ABSTRACT: The orphan nuclear receptor NR2F6 (Nuclear Receptor subfamily 2 group F member 6) is an emerging therapeutic target for cancer immunotherapy. Upregulation of NR2F6 expression in tumor cells has been linked to proliferation and metastasis, while in immune cells NR2F6 inhibits antitumor T-cell responses. Small molecule modulation of NR2F6 activity might therefore be a novel strategy in cancer treatment, benefiting from this dual role of NR2F6. However, there are no molecular strategies available for targeting NR2F6, hampered among others by lack of structural insights and appropriate biochemical assays. To overcome these challenges, several noncanonical nuclear receptor coregulator peptide motifs were identified to be constitutively recruited to the NR2F6 ligand binding domain (LBD). Co-crys

SUBMITTER: Oerlemans GJM 

PROVIDER: S-EPMC12455566 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature