title: Scaffolding during the cell cycle by A-kinase anchoring proteins.
abstract: Cell division relies on coordinated regulation of the cell cycle. A process including a well-defined series of strictly regulated molecular mechanisms involving cyclin-dependent kinases, retinoblastoma protein, and polo-like kinases. Dysfunctions in cell cycle regulation are associated with disease such as cancer, diabetes, and neurodegeneration. Compartmentalization of cellular signaling is a common strategy used to ensure the accuracy and efficiency of cellular responses. Compartmentalization of intracellular signaling is maintained by scaffolding proteins, such as A-kinase anchoring proteins (AKAPs). AKAPs are characterized by their ability to anchor the regulatory subunits of protein kinase A (PKA), and thereby achieve guidance to different cellular locations via various targeting domains. Next to PKA, AKAPs also associate with several other signaling elements including receptors, ion channels, protein kinases, phosphatases, small GTPases, and phosphodiesterases. Taking the amount of possible AKAP signaling complexes and their diverse localization into account, it is rational to believe that such AKAP-based complexes regulate several critical cellular events of the cell cycle. In fact, several AKAPs are assigned as tumor suppressors due to their vital roles in cell cycle regulation. Here, we first briefly discuss the most important players of cell cycle progression. After that, we will review our recent knowledge of AKAPs linked to the regulation and progression of the cell cycle, with special focus on AKAP12, AKAP8, and Ezrin. At last, we will discuss this specific AKAP subset in relation to diseases with focus on a diverse subset of cancer.
authors.affiliation: Department of Molecular Pharmacology, University of Groningen, Groningen, The Netherlands. b.han@rug.nl.|Groningen Research Institute for Asthma and COPD, GRIAC, Groningen, The Netherlands. b.han@rug.nl.
authors.forename: B
authors.initials: B
authors.lastname: Han
authors.affiliation: Department of Molecular Pharmacology, University of Groningen, Groningen, The Netherlands.|Groningen Research Institute for Asthma and COPD, GRIAC, Groningen, The Netherlands.
authors.forename: W J
authors.initials: WJ
authors.lastname: Poppinga
authors.affiliation: Department of Molecular Pharmacology, University of Groningen, Groningen, The Netherlands.|Groningen Research Institute for Asthma and COPD, GRIAC, Groningen, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Schmidt
mesh_terms: D054758:A Kinase Anchor Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002453:Cell Cycle; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D054758:A Kinase Anchor Proteins; D007473:Ion Channels; D017868:Cyclic AMP-Dependent Protein Kinases
keywords: AKAPs; Cancer; Cell cycle; Proliferation; Scaffolding