Abstract
Inherited mutations in the ATM gene lead to a complex clinical phenotype characterized by neuronal degeneration, oculocutaneous telangiectasias, immune dysfunction, and cancer predisposition. Using the yeast two-hybrid system, we demonstrate that ataxia telangiectasia mutated (ATM) binds to beta-adaptin, one of the components of the AP-2 adaptor complex, which is involved in clathrin-mediated endocytosis of receptors. The interaction between ATM and beta-adaptin was confirmed in vitro, and coimmunoprecipitation and colocalization studies show that the proteins also associate in vivo. ATM also interacts in vitro with beta-NAP, a neuronal-specific beta-adaptin homolog that was identified as an autoantigen in a patient with cerebellar degeneration. Our data describing the association of ATM with beta-adaptin in vesicles indicate that ATM may play a role in intracellular vesicle and/or protein transport mechanisms.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Protein Complex 3
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Adaptor Protein Complex beta Subunits
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Animals
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Ataxia Telangiectasia / etiology
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Ataxia Telangiectasia / genetics
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Ataxia Telangiectasia / metabolism
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Ataxia Telangiectasia Mutated Proteins
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Autoantigens / metabolism
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Base Sequence
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Cell Cycle Proteins
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Cerebellum / immunology
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Cerebellum / metabolism
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Cerebellum / pathology
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Chlorocebus aethiops
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Cytoplasm / metabolism
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DNA Primers / genetics
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DNA-Binding Proteins
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Humans
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In Vitro Techniques
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Membrane Proteins / metabolism*
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Mice
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Nerve Tissue Proteins / immunology
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Nerve Tissue Proteins / metabolism
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Peptide Fragments / genetics
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Peptide Fragments / metabolism
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Phosphoproteins / immunology
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Phosphoproteins / metabolism
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Protein Binding
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Protein Serine-Threonine Kinases*
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Proteins / genetics
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Proteins / metabolism*
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae / metabolism
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Transfection
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Tumor Suppressor Proteins
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Vero Cells
Substances
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AP3B2 protein, human
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Adaptor Protein Complex 3
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Adaptor Protein Complex beta Subunits
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Autoantigens
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Cell Cycle Proteins
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DNA Primers
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DNA-Binding Proteins
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Membrane Proteins
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Nerve Tissue Proteins
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Peptide Fragments
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Phosphoproteins
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Proteins
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Tumor Suppressor Proteins
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ATM protein, human
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Ataxia Telangiectasia Mutated Proteins
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Atm protein, mouse
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Protein Serine-Threonine Kinases