@article{3f87e9c4352747e7914338ac70d9bcac,
title = "The cell-cycle regulatory protein Cks1 is required for SCFSkp2-mediated ubiquitinylation of p27",
abstract = "The cyclin-dependent kinase (CDK) inhibitor p27 is degraded in late G1 phase by the ubiquitin pathway1, allowing CDK activity to drive cells into S phase2. Ubiquitinylation of p27 requires its phosphorylation at Thr 187 (refs 3, 4) and subsequent recognition by S-phase kinase associated protein 2 (Skp2; refs 5-8), a member of the F-box family of proteins that associates with Skp1, Cul-1 and ROC1/Rbx1 to form an SCF ubiquitin ligase complex9. However, in vitro ligation of p27 to ubiquitin could not be reconstituted by known purified components of the SCFSkp2 complex. Here we show that the missing factor is CDK subunit 1 (Cks1), which belongs to the highly conserved Suc1/Cks family of proteins that bind to some CDKs and phosphorylated proteins and are essential for cell-cycle progression. Human Cks1, but not other members of the family, reconstitutes ubiquitin ligation of p27 in a completely purified system, binds to Skp2 and greatly increases binding of T187-phosphorylated p27 to Skp2. Our results represent the first evidence that an SCF complex requires an accessory protein for activity as well as for binding to its phosphorylated substrate.",
author = "Dvora Ganoth and Gil Bornstein and Ko, {Tun K.} and Brett Larsen and Mike Tyers and Michele Pagano and Avram Hershko",
note = "Funding Information: ACKNOWLEDGEMENTS We thank C. Segal for technical assistance, S. Reed for sharing results before publication, Z-P. Pan, J. Pines, C. Pickart, S. Reed and E. Yeh for reagents, R. Piva and A. Carrano for their contribution to this work, and J. Bloom and L. Yamasaki for critical reading of the manuscript. M.P. also thanks L. Yamasaki and L. Bragi for their continuous support. This work was supported by grants from the Israel Science Foundation and the Human Frontier Science Program Organization (HFSPO; to A.H.), by an Irma T. Hirschl Scholarship and grants from the HFSPO and the NIH (to M.P), and by grants from the National Cancer Institute of Canada (to M.T). Part of this work was done during the stay of A.H. at New York Univ. Sch. Med. (on sabbatical leave), where he was supported by a UICC Yamagiwa–Yoshida Memorial International Cancer Study Grant. Correspondence and requests for materials should be addressed to M.P.. Supplementary Information is available on Nature Cell Biology{\textquoteright}s website (http://cellbio.nature.com) or as paper copy from the London editorial office of Nature Cell Biology.",
year = "2001",
doi = "10.1038/35060126",
language = "אנגלית",
volume = "3",
pages = "321--324",
journal = "Nature Cell Biology",
issn = "1465-7392",
publisher = "Nature Research",
number = "3",
}