Degradation of LMO2 in T cell leukaemia results in collateral breakdown of transcription complex partners and causes LMO2-dependent apoptosis.

ABSTRACT: LMO2 is an intrinsically disordered transcription factor activated in T cell leukaemia that is difficult to target. It forms part of a multi-protein complex that has bipartite DNA binding through heterodimeric basic-helix-loop-helix (bHLH) and GATA proteins. To determine if degradation of LMO2 in the context of T cell acute leukaemias (T-ALL) has therapeutic potential, a chimeric intracellular antibody has been developed fusing an anti-LMO2 single-domain variable region with one of three E3 ligases to create biodegraders. The intracellular binary interaction of these biodegraders with LMO2 leads to its proteasomal degradation but, in addition, concomitant loss of bHLH proteins that associate with LMO2 in the DNA-binding complex. Chemical compound surrogates of the intracellular antibody pa

SUBMITTER: Sereesongsaeng N 

PROVIDER: S-EPMC12700530 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature