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Label-Free Immunoprecipitation Mass Spectrometry Workflow for Large-scale Nuclear Interactome Profiling
Published on: November 17, 2019
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DYRK1A regulates Hap1-Dcaf7/WDR68 binding with implication for delayed growth in Down syndrome
Jianxing Xiang1, Su Yang1, Ning Xin1
1Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322.
Summary
Huntingtin-associated protein 1 (Hap1) regulates Dcaf7, impacting postnatal growth. Targeting Hap1 or Dcaf7 may help growth retardation in Down syndrome.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Huntingtin-associated protein 1 (Hap1) is vital for postnatal hypothalamic function and growth.
- Hap1 forms stigmoid bodies (SBs) in hypothalamic neurons, but their function is unclear.
Purpose of the Study:
- To identify Hap1-interacting proteins within SBs.
- To elucidate the role of Hap1, Dcaf7, and DYRK1A in postnatal growth and Down syndrome.
Main Methods:
- Developed a method to isolate SB-enriched fractions from mouse brain.
- Performed Hap1 immunoprecipitation and analyzed interacting proteins.
- Utilized transgenic Down syndrome mouse models and hypothalamic overexpression studies.
Main Results:
- Identified DDB1 and CUL4 associated factor 7 (Dcaf7) as a Hap1-interacting SB component.
- Hap1 regulates Dcaf7 protein levels and nuclear translocation.
- Hap1 competitively binds Dcaf7 with DYRK1A; Hap1 depletion enhances DYRK1A-Dcaf7 interaction and DYRK1A levels.
- DYRK1A overexpression in Down syndrome mice reduces Hap1-Dcaf7 association and causes delayed postnatal growth.
Conclusions:
- DYRK1A influences the Hap1-Dcaf7 interaction and postnatal growth.
- Targeting Hap1 or Dcaf7 may offer therapeutic potential for growth retardation in Down syndrome.
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