Deakin University
Browse
cheung-proteinsetbinds-2002.pdf (499.01 kB)

The protein SET binds the neuronal Cdk5 activator p35(nck5a) and modulates Cdk5/p35(nck5a) activity

Download (499.01 kB)
Version 2 2024-06-13, 10:39
Version 1 2017-08-03, 11:52
journal contribution
posted on 2024-06-13, 10:39 authored by D Qu, Q Li, H-Y Lim, NS Cheung, R Li, JH Wang, RZ Qi
The neuronal Cdk5 kinase is composed of the catalytic subunit Cdk5 and the activator protein p35(nck5a) or its isoform, p39(nck5ai). To identify novel p35(nck5a)- and p39(nck5ai)-binding proteins, fragments of p35(nck5a) and p39(nck5ai) were utilized in affinity isolation of binding proteins from rat brain homogenates, and the isolated proteins were identified using mass spectrometry. With this approach, the nuclear protein SET was shown to interact with the N-terminal regions of p35(nck5a) and p39(nck5ai). Our detailed characterization showed that the SET protein formed a complex with Cdk5/p35(nck5a) through its binding to p35(nck5a). The p35(nck5a)-interacting region was mapped to a predicted alpha-helix in SET. When cotransfected into COS-7 cells, SET and p35(nck5a) displayed overlapping intracellular distribution in the nucleus. The nuclear co-localization was corroborated by immunostaining data of endogenous SET and Cdk5/p35(nck5a) from cultured cortical neurons. Finally, we demonstrated that the activity of Cdk5/p35(nck5a), but not that of Cdk5/p25(nck5a), was enhanced upon binding to the SET protein. The tail region of SET, which is rich in acidic residues, is required for the stimulatory effect on Cdk5/p35(nck5a).

History

Journal

Journal of biological chemistry

Volume

277

Pagination

7324-7332

Location

Rockville, Md.

Open access

  • Yes

ISSN

0021-9258

eISSN

1083-351X

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal

Copyright notice

2002, The American Society for Biochemistry and Molecular Biology, Inc.

Issue

9

Publisher

American Society for Biochemistry and Molecular Biology