Multisite phosphorylation of a CDK inhibitor sets a threshold for the onset of DNA replication - PubMed (original) (raw)
. 2001 Nov 29;414(6863):514-21.
doi: 10.1038/35107009.
Affiliations
- PMID: 11734846
- DOI: 10.1038/35107009
Multisite phosphorylation of a CDK inhibitor sets a threshold for the onset of DNA replication
P Nash et al. Nature. 2001.
Abstract
SCF ubiquitin ligases target phosphorylated substrates for ubiquitin-dependent proteolysis by means of adapter subunits called F-box proteins. The F-box protein Cdc4 captures phosphorylated forms of the cyclin-dependent kinase inhibitor Sic1 for ubiquitination in late G1 phase, an event necessary for the onset of DNA replication. The WD40 repeat domain of Cdc4 binds with high affinity to a consensus phosphopeptide motif (the Cdc4 phospho-degron, CPD), yet Sic1 itself has many sub-optimal CPD motifs that act in concert to mediate Cdc4 binding. The weak CPD sites in Sic1 establish a phosphorylation threshold that delays degradation in vivo, and thereby establishes a minimal G1 phase period needed to ensure proper DNA replication. Multisite phosphorylation may be a more general mechanism to set thresholds in regulated protein-protein interactions.
Comment in
- Six steps to destruction.
Ferrell JE Jr. Ferrell JE Jr. Nature. 2001 Nov 29;414(6863):498-9. doi: 10.1038/35107180. Nature. 2001. PMID: 11734834 No abstract available.
Similar articles
- Structure of a Fbw7-Skp1-cyclin E complex: multisite-phosphorylated substrate recognition by SCF ubiquitin ligases.
Hao B, Oehlmann S, Sowa ME, Harper JW, Pavletich NP. Hao B, et al. Mol Cell. 2007 Apr 13;26(1):131-43. doi: 10.1016/j.molcel.2007.02.022. Mol Cell. 2007. PMID: 17434132 - Structural basis for phosphodependent substrate selection and orientation by the SCFCdc4 ubiquitin ligase.
Orlicky S, Tang X, Willems A, Tyers M, Sicheri F. Orlicky S, et al. Cell. 2003 Jan 24;112(2):243-56. doi: 10.1016/s0092-8674(03)00034-5. Cell. 2003. PMID: 12553912 - Transferable domain in the G(1) cyclin Cln2 sufficient to switch degradation of Sic1 from the E3 ubiquitin ligase SCF(Cdc4) to SCF(Grr1).
Berset C, Griac P, Tempel R, La Rue J, Wittenberg C, Lanker S. Berset C, et al. Mol Cell Biol. 2002 Jul;22(13):4463-76. doi: 10.1128/MCB.22.13.4463-4476.2002. Mol Cell Biol. 2002. PMID: 12052857 Free PMC article. - Multisite phosphorylation and the countdown to S phase.
Deshaies RJ, Ferrell JE Jr. Deshaies RJ, et al. Cell. 2001 Dec 28;107(7):819-22. doi: 10.1016/s0092-8674(01)00620-1. Cell. 2001. PMID: 11779457 Review. - End of the line: proteolytic degradation of cyclin-dependent kinase inhibitors.
Sheaff RJ, Roberts JM. Sheaff RJ, et al. Chem Biol. 1996 Nov;3(11):869-73. doi: 10.1016/s1074-5521(96)90174-x. Chem Biol. 1996. PMID: 8939714 Review.
Cited by
- Calcineurin-mediated dephosphorylation stabilizes E2F1 protein by suppressing binding of the FBXW7 ubiquitin ligase subunit.
Sato Y, Habara M, Hanaki S, Masaki T, Tomiyasu H, Miki Y, Sakurai M, Morimoto M, Kobayashi D, Miyamoto T, Shimada M. Sato Y, et al. Proc Natl Acad Sci U S A. 2024 Oct 8;121(41):e2414618121. doi: 10.1073/pnas.2414618121. Epub 2024 Oct 3. Proc Natl Acad Sci U S A. 2024. PMID: 39361641 - The emerging and diverse roles of F-box proteins in spermatogenesis and male infertility.
Zhuang X, Ruan J, Zhou C, Li Z. Zhuang X, et al. Cell Regen. 2024 Jun 26;13(1):13. doi: 10.1186/s13619-024-00196-9. Cell Regen. 2024. PMID: 38918264 Free PMC article. Review. - Molecular insights and clinical implications for the tumor suppressor role of SCFFBXW7 E3 ubiquitin ligase.
Qi Y, Rezaeian AH, Wang J, Huang D, Chen H, Inuzuka H, Wei W. Qi Y, et al. Biochim Biophys Acta Rev Cancer. 2024 Sep;1879(5):189140. doi: 10.1016/j.bbcan.2024.189140. Epub 2024 Jun 21. Biochim Biophys Acta Rev Cancer. 2024. PMID: 38909632 Review. - F-box proteins and gastric cancer: an update from functional and regulatory mechanism to therapeutic clinical prospects.
Yang Y, Xie Q, Hu C, Xu J, Chen L, Li Y, Luo C. Yang Y, et al. Int J Med Sci. 2024 Jun 3;21(8):1575-1588. doi: 10.7150/ijms.91584. eCollection 2024. Int J Med Sci. 2024. PMID: 38903918 Free PMC article. Review. - NOTCH localizes to mitochondria through the TBC1D15-FIS1 interaction and is stabilized via blockade of E3 ligase and CDK8 recruitment to reprogram tumor-initiating cells.
Choi HY, Zhu Y, Zhao X, Mehta S, Hernandez JC, Lee JJ, Kou Y, Machida R, Giacca M, Del Sal G, Ray R, Eoh H, Tahara SM, Chen L, Tsukamoto H, Machida K. Choi HY, et al. Exp Mol Med. 2024 Feb;56(2):461-477. doi: 10.1038/s12276-024-01174-6. Epub 2024 Feb 27. Exp Mol Med. 2024. PMID: 38409448 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases