Evidence that GRIP, a PDZ-domain protein which is expressed in the embryonic forebrain, co-activates transcription with DLX homeodomain proteins.
The DLX homeodomain proteins control development of the basal ganglia and branchial arches. To identify co-factors that regulate DLX function we utilized the yeast two-hybrid assay, and found a DLX interacting protein (DIP2) which binds to the N-terminal region of DLX2 via a PDZ domain. DIP2 appears to be an alternatively spliced form of GRIP1, a protein known to bind AMPA glutamate receptors via PDZ domains. Thus, we named it GRIP1b. We provide evidence that GRIP1b can function as a transcriptional co-activator of DLX2 and DLX5. Glutamate receptors inhibit this co-activation. These results suggest that some PDZ proteins may regulate transcription via their interactions with homeodomain proteins. Furthermore, these results suggest a link between glutamate receptors, PDZ proteins and the DLX transcription factors, all of which are co-expressed in the developing basal ganglia.
Yu
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Nina Ireland Laboratory of Developmental Neurobiology, Center for Neurobiology and Psychiatry, Department of Psychiatry, 401 Parnassus Avenue, University of California at San Francisco, CA 94143-0984, USA.
Zerucha
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Ekker
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Rubenstein
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JL
D017398:Alternative Splicing / Q000502:physiology; D000818:Animals; D029681:Arabidopsis Proteins; D001479:Basal Ganglia / Q000196:embryology* / Q000502:physiology*; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000502:physiology; D005656:Fungal Proteins / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D051958:Nuclear Receptor Coactivator 2; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins; D018091:Receptors, AMPA / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation / Q000502:physiology; D020798:Two-Hybrid System Techniques; D015003:Yeasts
D029681:Arabidopsis Proteins; D003598:Cytoskeletal Proteins; C435711:DIP2 protein, Arabidopsis; D004268:DNA-Binding Proteins; C088334:Distal-less homeobox proteins; C501120:Dlx5 protein, mouse; C100597:Dlx6 protein, mouse; D005656:Fungal Proteins; C052130:GAL4 protein, S cerevisiae; D018398:Homeodomain Proteins; C498002:Ncoa2 protein, mouse; D051958:Nuclear Receptor Coactivator 2; D016601:RNA-Binding Proteins; D018091:Receptors, AMPA; D029701:Saccharomyces cerevisiae Proteins; C093661:Tes protein, mouse; D014157:Transcription Factors; C104723:glutamate receptor ionotropic, AMPA 3; C104722:glutamate receptor ionotropic, AMPA 2