@article{f762ea7c966949edb5231ea8e892f3fa,
title = "NIPA defines an SCF-type mammalian E3 ligase that regulates mitotic entry",
abstract = "The regulated oscillation of protein expression is an essential mechanism of cell cycle control. The SCF class of E3 ubiquitin ligases is involved in this process by targeting cell cycle regulatory proteins for degradation by the proteasome, with the F-box subunit of the SCF specifically recruiting a given substrate to the SCF core. Here we identify NIPA (nuclear interaction partner of ALK) as a human F-box-containing protein that defines an SCF-type E3 ligase (SCFNIPA) controlling mitotic entry. Assembly of this SCF complex is regulated by cell-cycle-dependent phosphorylation of NIPA, which restricts substrate ubiquitination activity to interphase. We show nuclear cyclin B1 to be a substrate of SCFNIPA. Inactivation of NIPA by RNAi results in nuclear accumulation of cyclin B1 in interphase, activation of cyclin B1-Cdk1 kinase activity, and premature mitotic entry. Thus, SCFNIPA-based ubiquitination may regulate S-phase completion and mitotic entry in the mammalian cell cycle.",
author = "Florian Bassermann and {Von Klitzing}, Christine and Silvia M{\"u}nch and Bai, {Ren Yuan} and Hiroyuki Kawaguchi and Morris, {Stephan W.} and Christian Peschel and Justus Duyster",
note = "Funding Information: We thank M. Pagano for the Cul1, Roc1, Skp1, and Skp2 baculoviruses and the Skp2 cDNA; and K. Nakayama for the hCdc4 cDNA. W. Krek kindly provided the pCMV-HA-ubiquitin construct and the Cul1 and Roc1 expression plasmids. T. Hunt and J. Pines are acknowledged for providing the Xenopus and human cyclin B1 cDNAs. Dr. Xiaoli Cui provided expert technical assistance. This work was supported by a grant from the Wilhelm Sander Stiftung to J.D., DFG SFB-456 grant to J.D. and F.B., a research grant from the Technical University of Munich (KKF 8732562) to F.B., National Institutes of Health (NIH) grant CA 69129 to S.W.M. and J.D., NCI Cancer Center CORE grant 21765, and by the American Lebanese Syrian Associated Charities (ALSAC) and St. Jude Children{\textquoteright}s Research Hospital (S.W.M. and H.K.). ",
year = "2005",
month = jul,
day = "15",
doi = "10.1016/j.cell.2005.04.034",
language = "English",
volume = "122",
pages = "45--57",
journal = "Cell",
issn = "0092-8674",
publisher = "Elsevier B.V.",
number = "1",
}