Regulation of the Werner helicase through a direct interaction with a subunit of protein kinase A

Duy T. Nguyen, Ilsa I. Rovira, Toren Finkel

Research output: Contribution to journalArticle

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 (RIβ) 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.

Original languageEnglish (US)
Pages (from-to)170-174
Number of pages5
JournalFEBS Letters
Volume521
Issue number1-3
DOIs
StatePublished - Jun 19 2002
Externally publishedYes

Fingerprint

Genomic Instability
Cyclic AMP-Dependent Protein Kinases
RecQ Helicases
Cyclic AMP-Dependent Protein Kinase Catalytic Subunits
Werner Syndrome
Inborn Genetic Diseases
Genetic Predisposition to Disease
Aging of materials
Cell Nucleus
Serum
Intercellular Signaling Peptides and Proteins
Yeasts
Yeast
Mutation
Genes
Cells
Neoplasms

Keywords

  • Aging
  • Helicases
  • RecQ
  • Signal transduction
  • Werner syndrome

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Regulation of the Werner helicase through a direct interaction with a subunit of protein kinase A. / Nguyen, Duy T.; Rovira, Ilsa I.; Finkel, Toren.

In: FEBS Letters, Vol. 521, No. 1-3, 19.06.2002, p. 170-174.

Research output: Contribution to journalArticle

Nguyen, Duy T. ; Rovira, Ilsa I. ; Finkel, Toren. / Regulation of the Werner helicase through a direct interaction with a subunit of protein kinase A. In: FEBS Letters. 2002 ; Vol. 521, No. 1-3. pp. 170-174.
@article{e67652a397f745a683f6ca48481a14b6,
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 (RIβ) 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.",
keywords = "Aging, Helicases, RecQ, Signal transduction, Werner syndrome",
author = "Nguyen, {Duy T.} and Rovira, {Ilsa I.} and Toren Finkel",
year = "2002",
month = "6",
day = "19",
doi = "10.1016/S0014-5793(02)02868-5",
language = "English (US)",
volume = "521",
pages = "170--174",
journal = "FEBS Letters",
issn = "0014-5793",
publisher = "Elsevier",
number = "1-3",

}

TY - JOUR

T1 - Regulation of the Werner helicase through a direct interaction with a subunit of protein kinase A

AU - Nguyen, Duy T.

AU - Rovira, Ilsa I.

AU - Finkel, Toren

PY - 2002/6/19

Y1 - 2002/6/19

N2 - 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 (RIβ) 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.

AB - 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 (RIβ) 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.

KW - Aging

KW - Helicases

KW - RecQ

KW - Signal transduction

KW - Werner syndrome

UR - http://www.scopus.com/inward/record.url?scp=0037134775&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037134775&partnerID=8YFLogxK

U2 - 10.1016/S0014-5793(02)02868-5

DO - 10.1016/S0014-5793(02)02868-5

M3 - Article

C2 - 12067711

AN - SCOPUS:0037134775

VL - 521

SP - 170

EP - 174

JO - FEBS Letters

JF - FEBS Letters

SN - 0014-5793

IS - 1-3

ER -