Live cell kinetic analysis of the LMO2/LDB1 leukemogenic protein 1 complex reveals a hierarchy of turnover with implications for complex assembly
Layer, J. H.; Christy, M.; Placek, L.; Unutmaz, D.; Guo, Y.; Dave, U.
Show abstract
Multisubunit protein complexes operate in many cellular functions. The LDB1/LMO2 macromolecular complex has been posited to be critical in hematopoietic stem and progenitor cell specification and in the development of acute leukemia. This complex is comprised of core subunits of LMO2 and LDB1 as well as bHLH and GATA transcription factors. We analyzed the steady state abundance and kinetic stability of LMO2 and its partners via HALO protein tagging in conjunction with variant proteins deficient in binding their respective direct protein partners. We discovered a hierarchy of protein stability, with half lives in descending order: LDB1>SSBP>LMO2>TAL1. Importantly, LDB1 conferred enhanced stability upon each and every subunit component and nucleated the formation of the multisubunit protein complex. Our studies provide significant insights into LDB1/LMO2 macromolecular protein complex assembly and stability, which has implications for understanding its role in blood cell formation and for therapeutically targeting this complex in human leukemias.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- A stress-induced Tyrosine tRNA depletion response mediates codon-based translational repression and growth suppression 93%
- Human CST complex protects replication fork stability by directly blocking MRE11 degradation of nascent strand DNA 93%
- An alternative UPF1 isoform drives conditional remodeling of nonsense-mediated mRNA decay 92%
Similar papers in this journal
Similar papers in this journal
- HAPSTR1 localizes HUWE1 to the nucleus to limit stress signaling pathways 93%
- USP9X deubiquitylates DVL2 to regulate WNT pathway specification 93%
- Derlin rhomboid pseudoproteases employ substrate engagement and lipid distortion function for retrotranslocation of ER multi-spanning membrane substrates 93%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.