Reconstitution of G
            <sub>1</sub>
            Cyclin Ubiquitination with Complexes Containing SCF
            <sup>Grr1</sup>
            and Rbx1

Skowyra, Dorota; Koepp, Deanna M.; Kamura, Takumi; Conrad, Michael N.; Conaway, Ronald C.; Conaway, Joan Weliky; Elledge, Stephen J.; Harper, J. Wade

doi:10.1126/science.284.5414.662

Cited by 364 publications

(299 citation statements)

References 23 publications

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“…These proteins contain a 180-residue domain referred to as the cullin homology domain (Zachariae et al, 1998b). As described above, the C-terminal cullin domain of Cdc53 binds to the RING-H2 finger protein Hrt1/Rbx1 that in turn binds to the E2 enzyme tethering this enzyme to the SCF Seol et al, 1999;Skowyra et al, 1999). The N-terminal domain of Cdc53 binds to Skp1, mediating the association with the Figure 3 Comparison of the APC Cdc20 and the SCF ubiquitinligases.…”

Section: Apc1mentioning

confidence: 99%

The anaphase-promoting complex: a key factor in the regulation of cell cycle

et al. 2005

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Events controlling cell division are governed by the degradation of different regulatory proteins by the ubiquitin-dependent pathway. In this pathway, the attachment of a polyubiquitin chain to a substrate by an ubiquitin-ligase targets this substrate for degradation by the 26S proteasome. Two different ubiquitin ligases play an important role in the cell cycle: the SCF (Skp1/Cullin/ F-box) and the anaphase-promoting complex (APC). In this review, we describe the present knowledge about the APC. We pay particular attention to the latest results concerning APC structure, APC regulation and substrate recognition, and we discuss the implication of these findings in the understanding the APC function.

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Section: Apc1mentioning

confidence: 99%

The anaphase-promoting complex: a key factor in the regulation of cell cycle

et al. 2005

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“…Similar SCF complexes containing cullin proteins have been found in mammals; they mediate the degradation of a variety of substrates, including I B and E2F (Marti et al, 1999;Tan et al, 1999). APC11 contains a Zn 2ϩ -binding motif referred to as the RING-H2 finger and is homologous to Rbx1/Roc1/ Hrt1 that physically interacts with Cul1 in mammals and Cdc53p in yeast (Zachariae et al, 1998;Kamura et al, 1999;Ohta et al, 1999;Seol et al, 1999;Skowyra et al, 1999;Gmachl et al, 2000). Because the Cul1/Rbx1 heterodimeric complex is the functional core of the SCF ubiquitin ligases, APC2 and APC11, by analogy, might also be directly involved in catalysis (Seol et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

“…No clues about the biochemical functions of most APC subunits can be inferred from examining their amino acid sequences. However, sequence analysis of APC2 and APC11 has revealed homology with proteins involved in other ubiquitination systems, particularly the Skp1-Cullin-F-box (SCF) pathway Zachariae et al, 1998;Deshaies, 1999;Ohta et al, 1999;Skowyra et al, 1999;Gmachl et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

APC2 Cullin Protein and APC11 RING Protein Comprise the Minimal Ubiquitin Ligase Module of the Anaphase-promoting Complex

Tang¹,

Li²,

Bharadwaj³

et al. 2001

MBoC

166

142

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In mitosis, the anaphase-promoting complex (APC) regulates the onset of sister-chromatid separation and exit from mitosis by mediating the ubiquitination and degradation of the securin protein and mitotic cyclins. With the use of a baculoviral expression system, we have reconstituted the ubiquitin ligase activity of human APC. In combination with Ubc4 or UbcH10, a heterodimeric complex of APC2 and APC11 is sufficient to catalyze the ubiquitination of human securin and cyclin B1. However, the minimal APC2/11 ubiquitin ligase module does not possess substrate specificity, because it also ubiquitinates the destruction box deletion mutants of securin and cyclin B1. Both APC11 and UbcH10 bind to the C-terminal cullin homology domain of APC2, whereas Ubc4 interacts with APC11 directly. Zn 2ϩ -binding and mutagenesis experiments indicate that APC11 binds Zn 2ϩ at a 1:3 M ratio. Unlike the two Zn 2ϩ ions of the canonical RING-finger motif, the third Zn 2ϩ ion of APC11 is not essential for its ligase activity. Surprisingly, with Ubc4 as the E2 enzyme, Zn 2ϩ ions alone are sufficient to catalyze the ubiquitination of cyclin B1. Therefore, the Zn 2ϩ ions of the RING finger family of ubiquitin ligases may be directly involved in catalysis.

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“…Members of the highly conserved SCF (Skp1/Cdc53/Fbox protein) ubiquitin ligase family have been shown to control cell proliferation by regulating the ubiquitin-mediated proteolysis of key cell cycle regulators Willems et al, 1996;Feldman et al, 1997;Skowyra et al, 1997Skowyra et al, , 1999Carrano et al, 1999;Tsvetkov et al, 1999;Strohmaier et al, 2001;Koepp et al, 2001). SCF complexes are modular ubiquitin ligases whose specificity is determined by a substrate-binding F-box protein (Feldman et al, 1997;Skowyra et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

The F-Box Protein Dia2 Regulates DNA Replication

Koepp

Kile

Swaminathan

et al. 2006

MBoC

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Ubiquitin-mediated proteolysis plays a key role in many pathways inside the cell and is particularly important in regulating cell cycle transitions. SCF (Skp1/Cul1/F-box protein) complexes are modular ubiquitin ligases whose specificity is determined by a substrate-binding F-box protein. Dia2 is a Saccharomyces cerevisiae F-box protein previously described to play a role in invasive growth and pheromone response pathways. We find that deletion of DIA2 renders cells cold-sensitive and subject to defects in cell cycle progression, including premature S-phase entry. Consistent with a role in regulating DNA replication, the Dia2 protein binds replication origins. Furthermore, the dia2 mutant accumulates DNA damage in both S and G2/M phases of the cell cycle. These defects are likely a result of the absence of SCF Dia2 activity, as a Dia2 ⌬F-box mutant shows similar phenotypes. Interestingly, prolonging G1-phase in dia2 cells prevents the accumulation of DNA damage in S-phase. We propose that Dia2 is an origin-binding protein that plays a role in regulating DNA replication.

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Reconstitution of G ₁ Cyclin Ubiquitination with Complexes Containing SCF ^Grr1 and Rbx1

Cited by 364 publications

References 23 publications

The anaphase-promoting complex: a key factor in the regulation of cell cycle

The anaphase-promoting complex: a key factor in the regulation of cell cycle

APC2 Cullin Protein and APC11 RING Protein Comprise the Minimal Ubiquitin Ligase Module of the Anaphase-promoting Complex

The F-Box Protein Dia2 Regulates DNA Replication

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Reconstitution of G 1 Cyclin Ubiquitination with Complexes Containing SCF Grr1 and Rbx1

Cited by 364 publications

References 23 publications

The anaphase-promoting complex: a key factor in the regulation of cell cycle

The anaphase-promoting complex: a key factor in the regulation of cell cycle

APC2 Cullin Protein and APC11 RING Protein Comprise the Minimal Ubiquitin Ligase Module of the Anaphase-promoting Complex

The F-Box Protein Dia2 Regulates DNA Replication

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Reconstitution of G ₁ Cyclin Ubiquitination with Complexes Containing SCF ^Grr1 and Rbx1