title: Regulation of the Werner helicase through a direct interaction with a subunit of protein kinase A.
abstract: Werner syndrome is a hereditary disease characterized by cancer predisposition, genetic instability, and the premature appearance of features associated with normal aging. At the molecular level this syndrome has been related to mutations in the Werner helicase, a member of the RecQ family of DNA helicases which are required to maintain genomic stability in cells. Here we show by a yeast two-hybrid screen that the Werner helicase can directly interact with the regulatory subunit (RIbeta) of cAMP protein kinase A (PKA). We confirm that this interaction occurs in vivo. Interestingly, serum withdrawal causes a redistribution of the Werner helicase within the nucleus of mammalian cells. Raising intracellular cAMP levels or increased expression of the regulatory but not the catalytic subunit of PKA inhibits this nuclear redistribution stimulated by serum deprivation. These results suggest that similar to lower organisms, gene products linked to genomic instability and aging may be directly regulated by growth factor-sensitive, PKA-dependent pathways.
authors.affiliation: Cardiovascular Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bldg 10/6N-240, 10 Center Drive, Bethesda, MD 20892-1622, USA.
authors.forename: Duy T
authors.initials: DT
authors.lastname: Nguyen
authors.forename: Ilsa I
authors.initials: II
authors.lastname: Rovira
authors.forename: Toren
authors.initials: T
authors.lastname: Finkel
mesh_terms: D001665:Binding Sites; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014898:Werner Syndrome / Q000201:enzymology*
chemical_list: D011993:Recombinant Fusion Proteins; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D004265:DNA Helicases