title: New partner proteins containing novel internal recognition motif for human glutaminase interacting protein (hGIP).
abstract: Regulation of gene expression in cells is mediated by protein-protein, DNA-protein and receptor-ligand interactions. PDZ (PSD-95/Discs-large/ZO-1) domains are protein-protein interaction modules. PDZ-containing proteins function in the organization of multi-protein complexes controlling spatial and temporal fidelity of intracellular signaling pathways. In general, PDZ proteins possess multiple domains facilitating distinct interactions. The human glutaminase interacting protein (hGIP) is an unusual PDZ protein comprising entirely of a single PDZ domain and plays pivotal roles in many cellular processes through its interaction with the C-terminus of partner proteins. Here, we report the identification by yeast two-hybrid screening of two new hGIP-interacting partners, DTX1 and STAU1. Both proteins lack the typical C-terminal PDZ recognition motif but contain a novel internal hGIP recognition motif recently identified in a phage display library screen. Fluorescence resonance energy transfer and confocal microscopy analysis confirmed the in vivo association of hGIP with DTX1 and STAU1 in mammalian cells validating the previous discovery of S/T-X-V/L-D as a consensus internal motif for hGIP recognition. Similar to hGIP, DTX1 and STAU1 have been implicated in neuronal function. Identification of these new interacting partners furthers our understanding of GIP-regulated signaling cascades and these interactions may represent potential new drug targets in humans.
authors: Department of Medical Biology, Faculty of Medicine, Pamukkale University, Denizli 20070, Turkey.
authors: Sevil
authors: S
authors: Zencir
authors: Monimoy
authors: M
authors: Banerjee
authors: Melanie J
authors: MJ
authors: Dobson
authors: Ferhan
authors: F
authors: Ayaydin
authors: Elfrieda Ayaydin
authors: EA
authors: Fodor
authors: Zeki
authors: Z
authors: Topcu
authors: Smita
authors: S
authors: Mohanty
mesh_terms: D020816:Amino Acid Motifs; D001921:Brain; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D005333:Fetus; D031541:Fluorescence Resonance Energy Transfer; D015723:Gene Library; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D054731:PDZ Domains; D025941:Protein Interaction Mapping; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
chemical_list: D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016601:RNA-Binding Proteins; C492185:STAU1 protein, human; C421249:TAX1BP3 protein, human; C583410:DTX1 protein, human; D044767:Ubiquitin-Protein Ligases
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