Editors' ChoiceCell Cycle

CSN5 Shuttles p27 Out of the Nucleus

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Science's STKE  22 Jan 2002:
Vol. 2002, Issue 116, pp. tw34
DOI: 10.1126/stke.2002.116.tw34

The cyclin-dependent kinase inhibitor p27 acts in early phases of the cell cycle. This protein is regulated by phosphorylation, subcellular localization, and degradation by the proteasome. Jab1 is a transcriptional regulator and is also part of the COP9 signalosome complex (and is thus also known as CSN5). CSN5 interacts with p27, and overexpression of CSN5 decreases the amount of p27 in cells. Tomoda et al. determined that CSN5 has a nuclear export signal and acts as an adaptor between p27 and the CRM1 nuclear transport receptor to promote p27 export from the nucleus and subsequent degradation. They identified a CSN5 binding motif in p27 that was essential for nuclear export and degradation, and found the same motif in other CSN5-interacting proteins. CSN5 existed in two distinct complexes in different cellular locations: in the COP9 signalosome in the nucleus and in a smaller complex of unknown components in the cytoplasm. Overexpression of certain other members of the COP9 signalosome increased the amount of CSN5 in the cytoplasm. The ability to induce the degradation of p27 was not limited to CSN5, but also occurred with overexpression of other COP9 signalosome subunits. Whether this is an effect on the signalosome complex or occurs through a direct interaction with p27 remains unknown.

K. Tomoda, Y. Kubota, Y. Arata, S. Mori, M. Maeda, T. Tanaka, M. Yoshida, N. Yoneda-Kato, J.-y. Kato, The cytoplasmic shuttling and subsequent degradation of p27Kip1 mediated by Jab1/CSN5 and the COP9 signalosome complex, J. Biol. Chem. 277, 2302-2310 (2002). [Abstract] [Full Text]

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