Previous Article | Next Article 
Molecular and Cellular Biology, March 1999, p. 1759-1767, Vol. 19, No. 3
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
The Abundance of Cell Cycle Regulatory Protein Cdc4p Is
Controlled by Interactions between Its F Box and Skp1p
Neal
Mathias,1,*
Steve
Johnson,2,
Breck
Byers,2 and
Mark
Goebl1
Department of Biochemistry and Molecular
Biology, Indiana University School of Medicine and the Walther
Oncology Center, Indianapolis, Indiana
46202-5122,1 and Department of
Genetics, University of Washington, Seattle, Washington
98195-73602
Received 10 August 1998/Returned for modification 21 September
1998/Accepted 5 December 1998
Posttranslational modification of a protein by ubiquitin usually
results in rapid degradation of the ubiquitinated protein by the
proteasome. The transfer of ubiquitin to substrate is a multistep
process. Cdc4p is a component of a ubiquitin ligase that tethers the
ubiquitin-conjugating enzyme Cdc34p to its substrates. Among the
domains of Cdc4p that are crucial for function are the F-box, which
links Cdc4p to Cdc53p through Skp1p, and the WD-40 repeats, which are
required for binding the substrate for Cdc34p. In addition to Cdc4p,
other F-box proteins, including Grr1p and Met30p, may similarly act
together with Cdc53p and Skp1p to function as ubiquitin ligase
complexes. Because the relative abundance of these complexes, known
collectively as SCFs, is important for cell viability, we have sought
evidence of mechanisms that modulate F-box protein regulation. Here we
demonstrate that the abundance of Cdc4p is subject to control by a
peptide segment that we term the R-motif (for "reduced abundance").
Furthermore, we show that binding of Skp1p to the F-box of Cdc4p
inhibits R-motif-dependent degradation of Cdc4p. These results suggest
a general model for control of SCF activities.
*
Corresponding author. Mailing address: Department of
Biochemistry and Molecular Biology, Indiana University School of
Medicine, 635 Barnhill Dr., Indianapolis, IN 46202-5122. Phone: (317)
274-3743. Fax: (317) 274-4686. E-mail:
neal{at}biochem4.iupui.edu.

Present address: Genetics Department, Washington University, St.
Louis, MO
63110.
Molecular and Cellular Biology, March 1999, p. 1759-1767, Vol. 19, No. 3
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
-
Scaglione, K. M., Bansal, P. K., Deffenbaugh, A. E., Kiss, A., Moore, J. M., Korolev, S., Cocklin, R., Goebl, M., Kitagawa, K., Skowyra, D.
(2007). SCF E3-Mediated Autoubiquitination Negatively Regulates Activity of Cdc34 E2 but Plays a Nonessential Role in the Catalytic Cycle In Vitro and In Vivo. Mol. Cell. Biol.
27: 5860-5870
[Abstract]
[Full Text]
-
Ivantsiv, Y., Kaplun, L., Tzirkin-Goldin, R., Shabek, N., Raveh, D.
(2006). Unique Role for the UbL-UbA Protein Ddi1 in Turnover of SCFUfo1 Complexes.. Mol. Cell. Biol.
26: 1579-1588
[Abstract]
[Full Text]
-
Liu, B., Sarkis, P. T. N., Luo, K., Yu, Y., Yu, X.-F.
(2005). Regulation of Apobec3F and Human Immunodeficiency Virus Type 1 Vif by Vif-Cul5-ElonB/C E3 Ubiquitin Ligase. J. Virol.
79: 9579-9587
[Abstract]
[Full Text]
-
Kim, J.-H., Kim, J., Kim, D.-H., Ryu, G.-H., Bae, S.-H., Seo, Y.-S.
(2004). SCFhFBH1 can act as helicase and E3 ubiquitin ligase. Nucleic Acids Res
32: 2287-2297
[Abstract]
[Full Text]
-
Li, Y., Gazdoiu, S., Pan, Z.-Q., Fuchs, S. Y.
(2004). Stability of Homologue of Slimb F-box Protein Is Regulated by Availability of Its Substrate. J. Biol. Chem.
279: 11074-11080
[Abstract]
[Full Text]
-
Michel, J. J., McCarville, J. F., Xiong, Y.
(2003). A Role for Saccharomyces cerevisiae Cul8 Ubiquitin Ligase in Proper Anaphase Progression. J. Biol. Chem.
278: 22828-22837
[Abstract]
[Full Text]
-
Dixon, C., Brunson, L. E., Roy, M. M., Smothers, D., Sehorn, M. G., Mathias, N.
(2003). Overproduction of Polypeptides Corresponding to the Amino Terminus of the F-Box Proteins Cdc4p and Met30p Inhibits Ubiquitin Ligase Activities of Their SCF Complexes. Eukaryot Cell
2: 123-133
[Abstract]
[Full Text]
-
Fung, T. K., Siu, W. Y., Yam, C. H., Lau, A., Poon, R. Y. C.
(2002). Cyclin F Is Degraded during G2-M by Mechanisms Fundamentally Different from Other Cyclins. J. Biol. Chem.
277: 35140-35149
[Abstract]
[Full Text]
-
Kamura, T., Brower, C. S., Conaway, R. C., Conaway, J. W.
(2002). A Molecular Basis for Stabilization of the von Hippel-Lindau (VHL) Tumor Suppressor Protein by Components of the VHL Ubiquitin Ligase. J. Biol. Chem.
277: 30388-30393
[Abstract]
[Full Text]
-
Hyman, L. E., Kwon, E., Ghosh, S., McGee, J., Chachulska, A. M. B., Jackson, T., Baricos, W. H.
(2002). Binding to Elongin C Inhibits Degradation of Interacting Proteins in Yeast. J. Biol. Chem.
277: 15586-15591
[Abstract]
[Full Text]
-
Kepinski, S., Leyser, O.
(2002). Ubiquitination and Auxin Signaling: A Degrading Story. Plant Cell
14: S81-95
[Full Text]
-
Smardon, A. M., Tarsio, M., Kane, P. M.
(2002). The RAVE Complex Is Essential for Stable Assembly of the Yeast V-ATPase. J. Biol. Chem.
277: 13831-13839
[Abstract]
[Full Text]
-
Gomes, M. D., Lecker, S. H., Jagoe, R. T., Navon, A., Goldberg, A. L.
(2001). Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy. Proc. Natl. Acad. Sci. USA
10.1073/pnas.251541198v1
[Abstract]
[Full Text]
-
Smothers, D. B., Kozubowski, L., Dixon, C., Goebl, M. G., Mathias, N.
(2000). The Abundance of Met30p Limits SCFMet30p Complex Activity and Is Regulated by Methionine Availability. Mol. Cell. Biol.
20: 7845-7852
[Abstract]
[Full Text]
-
Blondel, M., Galan, J.-M., Peter, M.
(2000). Isolation and Characterization of HRT1 Using a Genetic Screen for Mutants Unable to Degrade Gic2p in Saccharomyces cerevisiae. Genetics
155: 1033-1044
[Abstract]
[Full Text]
-
Block, K., Boyer, T. G., Yew, P. R.
(2001). Phosphorylation of the Human Ubiquitin-conjugating Enzyme, CDC34, by Casein Kinase 2. J. Biol. Chem.
276: 41049-41058
[Abstract]
[Full Text]
-
Gomes, M. D., Lecker, S. H., Jagoe, R. T., Navon, A., Goldberg, A. L.
(2001). Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy. Proc. Natl. Acad. Sci. USA
98: 14440-14445
[Abstract]
[Full Text]