Act Globally, Think Locally: Systems Biology Addresses the PDZ Domain

Spaller, Mark R.

doi:10.1021/cb600191y

Cited by 23 publications

(16 citation statements)

References 21 publications

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“…20 Recently, HPV viral oncoproteins have also been shown to interact and degrade key signaling components through interactions involving PDZ domains, a common structural domain of 80-90 amino acids found in many signaling proteins. 29 This structural motif is present in >400 proteins over 900 times in the human genome, 30 providing an incalculable advantage to viral disruption of normal signal transduction mechanisms. In fact, a functional class I PDZ-binding motif has been identified at the C-terminus of high-risk, but not low-risk, HPV E6 proteins.…”

Section: Mechanism Of Hpv-induced Carcinogenesismentioning

confidence: 99%

Biology of Human Papillomavirus–Related Oropharyngeal Cancer

Howard

Chung

2012

Seminars in Radiation Oncology

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Recent data show that human papillomavirus–positive oropharyngeal cancer (OPC) has a distinct biological and clinical behavior compared with human papillomavirus–negative OPC. As this subset of head and neck cancer represents an increasing public health concern, a thorough understanding of the causative and mechanistic differences between these diseases and how these distinctions impact clinical treatment is required. In this review, we will summarize recent data in epidemiology, the mechanism of viral carcinogenesis and differences in tumor biology that may provide insights to improve the clinical management of patients with human papillomavirus–positive OPC.

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Section: Mechanism Of Hpv-induced Carcinogenesismentioning

confidence: 99%

Biology of Human Papillomavirus–Related Oropharyngeal Cancer

Howard

Chung

2012

Seminars in Radiation Oncology

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“…In the mouse genome, for example, 928 PDZ domains have been recognized in 328 proteins, which exist in single or multiple copies or in combination with other interaction modules (Figure 1) [7]. From the abundance and diversity of PDZ domains in cells it is apparent that many cellular and biological functions, especially those involving signal transduction complexes, are affected by PDZ-mediated interactions [7-20]. …”

Section: Introductionmentioning

confidence: 99%

PDZ domains and their binding partners: structure, specificity, and modification

2010

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PDZ domains are abundant protein interaction modules that often recognize short amino acid motifs at the C-termini of target proteins. They regulate multiple biological processes such as transport, ion channel signaling, and other signal transduction systems. This review discusses the structural characterization of PDZ domains and the use of recently emerging technologies such as proteomic arrays and peptide libraries to study the binding properties of PDZ-mediated interactions. Regulatory mechanisms responsible for PDZ-mediated interactions, such as phosphorylation in the PDZ ligands or PDZ domains, are also discussed. A better understanding of PDZ protein-protein interaction networks and regulatory mechanisms will improve our knowledge of many cellular and biological processes.

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“…PDZ domains are small protein-protein interaction motifs that contain 80-100 amino acid residues. They form a compact domain primarily composed of 1-2 α-helices and 5-6 β-strands, and can be found in animal species, with homologous domains also observed in yeast and plants (7, 8). Proteins containing PDZ domains are often involved in signaling pathways and act as scaffolds in the organization of multimeric complexes, frequently in tandem with other protein-protein interaction modules (5).…”

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confidence: 99%

Promiscuous Binding at the Crossroads of Numerous Cancer Pathways: Insight from the Binding of Glutaminase Interacting Protein with Glutaminase L

et al. 2011

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The Glutaminase Interacting Protein (GIP) is composed of a single PDZ domain that interacts with a growing list of partner proteins, including Glutaminase L, that are involved in a number of cell signaling and cancer pathways. Therefore, GIP makes a good target for structure-based drug design. Here we report the solution structures of both free GIP and GIP bound to the C-terminal peptide analog of Glutaminase L. This is the first reported NMR structure of GIP in a complex with one of its binding partners. Our analysis of both free GIP and GIP complexed with the Glutaminase L peptide provides important insights into how a promiscuous binding domain can have affinity for multiple binding partners. Through a detailed chemical shift perturbation analysis and backbone dynamics studies, we demonstrate here that the binding of the Glutaminase L peptide to GIP is an allosteric event. Taken together, the insights reported here lay the groundwork for the future development of a specific inhibitor for GIP.

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Act Globally, Think Locally: Systems Biology Addresses the PDZ Domain

Abstract: hances are you have a favorite protein (or know someone who does), upon which research atten-*To whom correspondence should be addressed.

Cited by 23 publications

References 21 publications

Biology of Human Papillomavirus–Related Oropharyngeal Cancer

Biology of Human Papillomavirus–Related Oropharyngeal Cancer

PDZ domains and their binding partners: structure, specificity, and modification

Promiscuous Binding at the Crossroads of Numerous Cancer Pathways: Insight from the Binding of Glutaminase Interacting Protein with Glutaminase L

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