Huntingtin-Interacting Protein 1 Phosphorylation by Receptor Tyrosine Kinases

Ames, Heather M.; Wang, Anmin A.; Coughran, Alanna; Evaul, Kristen; Graves, Chiron W.; Soyombo, Abigail A.; Ross, Theodora S.

doi:10.1128/mcb.00473-13

Cited by 9 publications

(8 citation statements)

References 45 publications

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“…Knockdown of Dab2 accelerates the internalization rate of TLR4 and increases the amount of internalized TLR4 following stimulation of macrophages by LPS. The concept of a “clathrin sponge” has been proposed previously on the basis of the findings that huntingtin-interacting protein 1, which specifically binds clathrin, sequesters clathrin and acts as a clathrin sponge to prevent endocytosis of activated receptor tyrosine kinases to form endosomes in cancers 60 . Dab2 interacts with clathrin, and the interaction is diminished during mitosis, causing an increased internalization of the YXXØ type endocytic cargos 59 .…”

Section: Discussionmentioning

confidence: 99%

Disabled-2 is a negative immune regulator of lipopolysaccharide-stimulated Toll-like receptor 4 internalization and signaling

Hung¹,

Ling²,

Cheng

et al. 2016

Sci Rep

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Toll-like receptor 4 (TLR4) plays a pivotal role in the host response to lipopolysaccharide (LPS), a major cell wall component of Gram-negative bacteria. Here, we elucidated whether the endocytic adaptor protein Disabled-2 (Dab2), which is abundantly expressed in macrophages, plays a role in LPS-stimulated TLR4 signaling and trafficking. Molecular analysis and transcriptome profiling of RAW264.7 macrophage-like cells expressing short-hairpin RNA of Dab2 revealed that Dab2 regulated the TLR4/TRIF pathway upon LPS stimulation. Knockdown of Dab2 augmented TRIF-dependent interferon regulatory factor 3 activation and the expression of subsets of inflammatory cytokines and interferon-inducible genes. Dab2 acted as a clathrin sponge and sequestered clathrin from TLR4 in the resting stage of macrophages. Upon LPS stimulation, clathrin was released from Dab2 to facilitate endocytosis of TLR4 for triggering the TRIF-mediated pathway. Dab2 functions as a negative immune regulator of TLR4 endocytosis and signaling, supporting a novel role for a Dab2-associated regulatory circuit in controlling the inflammatory response of macrophages to endotoxin.

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Section: Discussionmentioning

confidence: 99%

Disabled-2 is a negative immune regulator of lipopolysaccharide-stimulated Toll-like receptor 4 internalization and signaling

Hung¹,

Ling²,

Cheng

et al. 2016

Sci Rep

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“…100 μg of total protein was electrophoresed on 6% SDS-PAGE gels, and transferred to a PVDF membrane. Proteins were detected with anti-Brca1 antiserum (1:100; GH118, kind gift of Dr. Jos Jonkers), mouse monoclonal anti-Hip1 (1:1000; 1B11, Ross laboratory (Ames et al, 2013)) and rabbit polyclonal anti-γH2AX (1:1000, Cell Signaling). Blots were developed with Supersignal West Pico chemiluminescence substrate (Pierce).…”

Section: Methodsmentioning

confidence: 99%

Distinct Brca1 Mutations Differentially Reduce Hematopoietic Stem Cell Function

et al. 2017

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BRCA1 is a well-known DNA repair pathway component and a tissue-specific tumor suppressor. However, its role in hematopoiesis is uncertain. Here we report that a cohort of patients heterozygous for BRCA1 mutations experienced more hematopoietic toxicity from chemotherapy than those with BRCA2 mutations. To test whether this reflects a requirement for BRCA1 in hematopoiesis, we generated mice with Brca1 mutations in hematopoietic cells. Mice homozygous for a null Brca1 mutation in the embryonic hematopoietic system (Vav1-iCre;Brca1F22–24/F22-24) developed hematopoietic defects in early adulthood that included reduced hematopoietic stem cells (HSCs). Although mice homozygous for a huBRCA1 knock-in allele (Brca1BRCA1/BRCA1) were normal, mice with a mutant huBRCA1/5382insC allele and a null allele (Mx1-Cre;Brca1F22-24/5382insC), had severe hematopoietic defects marked by a complete loss of hematopoietic stem and progenitor cells. Our data show that Brca1 is necessary for HSC maintenance and normal hematopoiesis, and that distinct mutations lead to different degrees of hematopoietic dysfunction.

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“…As four tyrosines in the human HIP1 ortholog were previously reported to be phosphorylated by the receptor tyrosine kinase epidermal growth factor receptor ( 23 ) and this phosphorylation was important for cell survival, we investigated whether phosphorylation of the analogous tyrosines in C. elegans HIPR-1 affects Orsay virus infection. As three of these tyrosines were conserved in HIPR-1, we engineered a triple tyrosine-to-phenylalanine (Y-F) nonphosphorylatable mutant form of HIPR-1 ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Mice deficient in both HIP1 and HIP1R exhibited aggravated spinal abnormalities and dwarfism, suggesting existence of a compensatory role of HIP1 and HIP1R ( 21 ). HIP proteins may be more functionally diverse than previously described, as studies in human cell culture have also suggested human HIP proteins may play a role in other cellular pathways such as androgen receptor transcription and apoptosis ( 22 , 23 ). Only a few studies have investigated the potential role of mammalian HIP1 and HIP1R in virus infection ( 24 – 26 ).…”

mentioning

confidence: 95%

Huntingtin-interacting protein family members have a conserved pro-viral function from Caenorhabditis elegans to humans

Jiang

Prado

Leung

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Huntingtin-interacting protein family members are evolutionarily conserved from yeast to humans, and they are known to be key factors in clathrin-mediated endocytosis. Here we identified the Caenorhabditis elegans protein huntingtin-interacting protein-related 1 (HIPR-1) as a host factor essential for Orsay virus infection of C. elegans. Ablation of HIPR-1 resulted in a greater than 10,000-fold reduction in viral RNA, which could be rescued by ectopic expression of HIPR-1. Viral RNA replication from an endogenous transgene replicon system was not affected by lack of HIPR-1, suggesting that HIPR-1 plays a role during an early, prereplication virus life-cycle stage. Ectopic expression of HIPR-1 mutants demonstrated that neither the clathrin light chain-binding domain nor the clathrin heavy chain-binding motif were needed for virus infection, whereas the inositol phospholipid-binding and F-actin–binding domains were essential. In human cell culture, deletion of the human HIP orthologs HIP1 and HIP1R led to decreased infection by Coxsackie B3 virus. Finally, ectopic expression of a chimeric HIPR-1 harboring the human HIP1 ANTH (AP180 N-terminal homology) domain rescued Orsay infection in C. elegans, demonstrating conservation of its function through evolution. Collectively, these findings further our knowledge of cellular factors impacting viral infection in C. elegans and humans.

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Huntingtin-Interacting Protein 1 Phosphorylation by Receptor Tyrosine Kinases

Cited by 9 publications

References 45 publications

Disabled-2 is a negative immune regulator of lipopolysaccharide-stimulated Toll-like receptor 4 internalization and signaling

Disabled-2 is a negative immune regulator of lipopolysaccharide-stimulated Toll-like receptor 4 internalization and signaling

Distinct Brca1 Mutations Differentially Reduce Hematopoietic Stem Cell Function

Huntingtin-interacting protein family members have a conserved pro-viral function from Caenorhabditis elegans to humans

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