The abundance of cell cycle regulatory protein Cdc4p is controlled by interactions between its F box and Skp1p

Neal Mathias, Steve Johnson, Breck Byers, Mark Goebl

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1759-1767
Number of pages9
JournalMolecular and Cellular Biology
Volume19
Issue number3
StatePublished - Mar 1999

Fingerprint

Cell Cycle Proteins
Ubiquitin
F-Box Proteins
Ligases
Ubiquitinated Proteins
Ubiquitin-Conjugating Enzymes
Proteasome Endopeptidase Complex
Post Translational Protein Processing
Cell Survival
Peptides
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

The abundance of cell cycle regulatory protein Cdc4p is controlled by interactions between its F box and Skp1p. / Mathias, Neal; Johnson, Steve; Byers, Breck; Goebl, Mark.

In: Molecular and Cellular Biology, Vol. 19, No. 3, 03.1999, p. 1759-1767.

Research output: Contribution to journalArticle

@article{7dadbc45c906482dbd7984f1e03a1e38,
title = "The abundance of cell cycle regulatory protein Cdc4p is controlled by interactions between its F box and Skp1p",
abstract = "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.",
author = "Neal Mathias and Steve Johnson and Breck Byers and Mark Goebl",
year = "1999",
month = "3",
language = "English",
volume = "19",
pages = "1759--1767",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "3",

}

TY - JOUR

T1 - The abundance of cell cycle regulatory protein Cdc4p is controlled by interactions between its F box and Skp1p

AU - Mathias, Neal

AU - Johnson, Steve

AU - Byers, Breck

AU - Goebl, Mark

PY - 1999/3

Y1 - 1999/3

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0033055912&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033055912&partnerID=8YFLogxK

M3 - Article

C2 - 10022863

AN - SCOPUS:0033055912

VL - 19

SP - 1759

EP - 1767

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 3

ER -