Nuclear localization of Cdk5 is a key determinant in the postmitotic state of neurons.

Nuclear localization of Cdk5 is a key determinant in the postmitotic state of neurons. Research Abstract Details 

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Nuclear localization of Cdk5 is a key determinant in the postmitotic state of neurons. Abstract Text:

Cyclin-dependent kinase 5 (Cdk5) is a nontraditional Cdk that is primarily active in postmitotic neurons. Its best known substrates are cytoskeletal proteins. Less appreciated is its role in the maintenance of a postmitotic state. We show here that in cycling cells (NIH 3T3), the localization of Cdk5 changes from predominantly nuclear to cytoplasmic as cells reenter a cell cycle after serum starvation. Similarly, when beta-amyloid peptide is used to stimulate cultured primary neurons to reenter a cell cycle, they too show a loss of nuclear Cdk5. Blocking nuclear export pharmacologically abolishes cell cycle reentry in wild-type but not Cdk5(-/-) neurons, suggesting a Cdk5-specific effect. Cdk5 overexpression targeted to the nucleus of Cdk5(-/-) neurons effectively blocks the cell cycle, but cytoplasmic targeting is ineffective. Further, in both human Alzheimer's disease as well as in the R1.40 mouse Alzheimer's model and the E2f1(-/-) mouse, neurons expressing cell cycle markers consistently show reduced nuclear Cdk5. Thus, both in vivo and in vitro, neurons that reenter a cell cycle lose nuclear Cdk5. We propose that the nuclear Cdk5 plays an active role in allowing neurons to remain postmitotic as they mature and that loss of nuclear Cdk5 leads to cell cycle entry.

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Nuclear localization of Cdk5 is a key determinant in the postmitotic state of neurons. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 105

Page Numbers: 8772-7

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

ISSN: 1091-6490

DAY: 12

MONTH: 06

YEAR: 2008

Nuclear localization of Cdk5 is a key determinant in the postmitotic state of neurons. Information

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LANGUAGE: eng

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Grant and Affiliation Information for Nuclear localization of Cdk5 is a key determinant in the postmitotic state of neurons.

AFFILIATION: Department of Cell Biology and Neuroscience, Rutgers University, 604 Allison Road, Piscataway, NJ 08854.

Country: United States

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MEDLINETA: Proc Natl Acad Sci U S A

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