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July 30, 2026The Journal of Immunology

Intrinsically disordered sequence in the ZMIZ1 drives leukemic activity, regulates protein stability and biomolecular condensate formation 2253537

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Authors

FGFrancisco Gomez‐RiveraUniversity of MichiganJNJannaldo Nieves-SalvaUniversity of MichiganSKSarah KhanUniversity of Michigan

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Implication

Randomized trial reveals ZMIZ1 mutations drive T-ALL in children and adults, suggesting new therapeutic avenues.

Key Points

  • This research uncovers the role of the alanine-rich domain (ARD) in regulating ZMIZ1 protein levels and activity in T-cell acute lymphoblastic leukemia (T-ALL).
  • Cloned wild-type and mutant ZMIZ1 into retroviruses and transduced into ZMIZ1-deficient 8946 T-ALL cells.
  • Measured ZMIZ1 protein levels and stability in response to ARD mutations and proteasome inhibition.
  • T-ALL mutants exhibited increased ZMIZ1 protein levels; NEDDFSA mutant showed decreased levels (mRNA unchanged).
  • Deleting ARD raised ZMIZ1 abundance 2.5-fold, indicating ARD acts as a degron.
  • Proteasome inhibition increased ZMIZ1 levels, linking ARD degradation to proteasomal pathways.

Cite This Study

Gomez‐Rivera et al. (2026) studied this question.

synapsesocial.com/papers/6a6af51160e2b924d3ea0a61https://doi.org/10.1093/jimmun/vkag141.178
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Effects of ZMIZ1 mutations in newly defined early T-cell precursor leukemia2025
  2. 2Abstract 6057: The IKZF1 N159Y partial tandem duplication mutant drives chromatin remodeling, B-cell developmental defects and leukemia initiation2026
  3. 3ZMIZ1 promotes PAX6 ubiquitination through SMAD3 to drive the malignant progression of acute myeloid leukemia2026
  4. 4Genetic and functional analysis of ZMIZ1 in neurodevelopmental disorder with dysmorphic facies and distal skeletal anomalies (NEDDFSA): insights from muscle cells and signaling pathways2025
  5. 5Genetic and functional analysis of ZMIZ1 in neurodevelopmental disorder with dysmorphic facies and distal skeletal anomalies (NEDDFSA): insights from muscle cells and signaling pathways2025 · 2 citations