NIPA defines an SCF-type mammalian E3 ligase that regulates mitotic entry

Florian Bassermann; Christine Von Klitzing; Silvia Münch; Ren Yuan Bai; Hiroyuki Kawaguchi; Stephan W. Morris; Christian Peschel; Justus Duyster

doi:10.1016/j.cell.2005.04.034

NIPA defines an SCF-type mammalian E3 ligase that regulates mitotic entry

Florian Bassermann, Christine Von Klitzing, Silvia Münch, Ren Yuan Bai, Hiroyuki Kawaguchi, Stephan W. Morris, Christian Peschel, Justus Duyster

Research output: Contribution to journal › Article › peer-review

56 Scopus citations

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 (SCF^NIPA) 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 SCF^NIPA. 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, SCF^NIPA-based ubiquitination may regulate S-phase completion and mitotic entry in the mammalian cell cycle.

Original language	English (US)
Pages (from-to)	45-57
Number of pages	13
Journal	Cell
Volume	122
Issue number	1
DOIs	https://doi.org/10.1016/j.cell.2005.04.034
State	Published - Jul 15 2005
Externally published	Yes

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.cell.2005.04.034

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@article{e155e59a12d349f282de02dd9e9c0ee9,

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 (US)",

volume = "122",

pages = "45--57",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

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TY - JOUR

T1 - NIPA defines an SCF-type mammalian E3 ligase that regulates mitotic entry

AU - Bassermann, Florian

AU - Von Klitzing, Christine

AU - Münch, Silvia

AU - Bai, Ren Yuan

AU - Kawaguchi, Hiroyuki

AU - Morris, Stephan W.

AU - Peschel, Christian

AU - Duyster, Justus

N1 - 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’s Research Hospital (S.W.M. and H.K.).

PY - 2005/7/15

Y1 - 2005/7/15

N2 - 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.

AB - 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.

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U2 - 10.1016/j.cell.2005.04.034

DO - 10.1016/j.cell.2005.04.034

M3 - Article

C2 - 16009132

AN - SCOPUS:22144495367

SN - 0092-8674

VL - 122

SP - 45

EP - 57

JO - Cell

JF - Cell

IS - 1

ER -

NIPA defines an SCF-type mammalian E3 ligase that regulates mitotic entry

Abstract

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