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Identification of nuclear import mechanisms for the neuronal Cdk5 activator

journal contribution
posted on 2023-05-17, 01:43 authored by Fu, X, Choi, YK, Qu, D, Yu, Y, Cheung, NS, Qi, RZ
The activation of Cdk5 by p35 plays a pivotal role in a multitude of nervous system activities ranging from neuronal differentiation to degeneration. A fraction of Cdk5 and p35 localizes in the nucleus where Cdk5-p35 exerts its functions via protein phosphorylation, and p35 displays a dynamic localization between the cytoplasm and the nucleus. Here, we examined the nuclear import properties of p35. In nuclear import assays, p35 was actively transported into the nuclei of digitonin-permeabilized HeLa cells and cortical neurons by cytoplasmic carrier-mediated mechanisms. Importin-â, importin-5, and importin-7 were identified to import p35 into the nuclei via a direct interaction with it. An N-terminal region of p35 was defined to interact with the above importins, serving as a nuclear localization signal. Finally, we show that the nuclear localization of p35 does not require the association of Cdk5. Furthermore, Cdk5 and importin-â/5/7 are mutually exclusive in binding to p35. These results suggest that p35 employs pathways distinct from that used by Cdk5 for transport to the nucleus.

History

Publication title

Journal of Biological Chemistry

Volume

281

Issue

51

Pagination

39014-39021

ISSN

0021-9258

Department/School

Menzies Institute for Medical Research

Publisher

Amer Soc Biochemistry Molecular Biology Inc

Place of publication

9650 Rockville Pike, Bethesda, USA, Md, 20814-3996

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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