Cdc42 GTPase-activating protein deficiency promotes genomic instability and premature aging-like phenotypes.

Cdc42 GTPase-activating protein deficiency promotes genomic instability and premature aging-like phenotypes. Research Abstract Details 

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Cdc42 GTPase-activating protein deficiency promotes genomic instability and premature aging-like phenotypes. Abstract Text:

Lei Wang,Linda Yang,Marcella Debidda,David Witte,Yi Zheng,

Cdc42 is a member of the Rho GTPase family known to regulate cell actin cytoskeleton organization, polarity, and growth, but its function in mammalian organismal physiology remains unclear. We found that natural aging of WT mice is marked with increased Cdc42 activity in various tissues. Among the negative regulators of Cdc42, gene targeting of Cdc42 GTPase-activating protein (Cdc42GAP) results in constitutively elevated Cdc42-GTP level in diverse tissues of adult mice; significantly shortened life span of the animals; and multiple premature aging-like phenotypes, including a reduction in body mass, a loss of subdermal adipose tissue, severe lordokyphosis, muscle atrophy, osteoporosis, and reduction of reepithelialization ability in wound-healing. Cdc42GAP-/- mouse embryonic fibroblasts and/or tissues display reduced population doubling, significantly dampened DNA damage repair activity after DNA-damaging agent treatment, accumulated genomic abnormalities, and induction of p53, p16Ink4a, p21Cip1, and senescence-associated beta-galactosidase expressions. Furthermore, Cdc42 activation is sufficient to promote a premature cellular senescence phenotype that depends on p53. These results suggest a role of Cdc42 activity in regulating mammalian genomic stability and aging-related physiology.

Cdc42 GTPase-activating protein deficiency promotes genomic instability and premature aging-like phenotypes. Publishing Authors By Initials

L Wang,L Yang,M Debidda,D Witte,Y Zheng,

For similar enzymes and coenzymes: enzymes: hydrolases: acid anhydride hydrolases: gtp phosphohydrolases: gtp-binding proteins: monomeric gtp-binding proteins: rho gtp-binding proteins: cdc42 gtp-binding protein research abstracts see: enzymes and coenzymes: enzymes: hydrolases: acid anhydride hydrolases: gtp phosphohydrolases: gtp-binding proteins: monomeric gtp-binding proteins: rho gtp-binding proteins: cdc42 gtp-binding protein research

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Cdc42 GTPase-activating protein deficiency promotes genomic instability and premature aging-like phenotypes. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 104

Page Numbers: 1248-53

Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

ISSN: 0027-8424

DAY: 16

MONTH: 01

YEAR: 2007

Cdc42 GTPase-activating protein deficiency promotes genomic instability and premature aging-like phenotypes. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7505876

Cdc42 GTPase-activating protein deficiency promotes genomic instability and premature aging-like phenotypes. Keywords Mesh Terms:

KEYWORDS: cdc42 GTP-Binding Protein

MESH TERMS: genetics

Chemical & Substance for Abstract: Cdc42 GTPase-activating protein deficiency promotes genomic instability and premature aging-like phenotypes. Information

Substance Name: cdc42 GTP-Binding Protein

Registry Number: EC 3.6.5.2

Grant and Affiliation Information for Cdc42 GTPase-activating protein deficiency promotes genomic instability and premature aging-like phenotypes.

AFFILIATION: Division of Experimental Hematology, Molecular Developmental Biology Graduate Program, Children's Hospital Research Foundation, University of Cincinnati, Cincinnati, OH 45229, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: GM53943

ACRONYM: GM

MEDLINETA: Proc Natl Acad Sci U S A

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