Cdc53/cullin and the essential Hrt1 RING-H2 subunit of SCF define a ubiquitin ligase module that activates the E2 enzyme Cdc34

Seol, Jae Hong; Feldman, R. M. Renny; Zachariae, Wolfgang; Shevchenko, Anna; Correll, Craig C.; Lyapina, Svetlana; Chi, Yong; Gálová, Marta; Claypool, Joshua T.; Sandmeyer, Suzanne; Nasmyth, Kim; Deshaies, Raymond J.

doi:10.1101/gad.13.12.1614

Cited by 374 publications

(370 citation statements)

References 54 publications

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“…It might stabilize the oxyanion of the putative tetrahedral intermediate of the reaction. Along this line, it is worth noting that polycations can stimulate the autoubiquitination activity of Cdc34, and the polycations have been proposed to stabilize the oxyanion intermediate (Seol et al, 1999;Zachariae and Nasmyth, 1999). Zn 2ϩ might also promote the release of the active thiol group of the E2 from the tetrahedral intermediate.…”

Section: Role Of Zn 2؉ Ions In Catalysismentioning

confidence: 99%

“…The minimal ligase modules of APC and other cullin-RING type of E3s appear to be constitutively active, at least in vitro (Seol et al, 1999). The regulation of the ubiquitination processes involving these enzymes resides in substrate binding.…”

Section: Substrate Recognition By Apc and Its Regulation During Cell mentioning

confidence: 99%

“…However, this does not seem to be the prevailing mechanism for all ubiquitination reactions. For the SCF complexes, it appears that the ubiquitination reactions do not involve the formation of an E3-ubiquitin thioester (Seol et al, 1999). Instead, the SCF complexes serve as a scaffold to bring together the E2 enzyme Cdc34 and the substrates.…”

Section: Mechanism Of Ubiquitin Transfer Of Apc-catalyzed Reactionsmentioning

confidence: 99%

“…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%

“…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). In fact, it has recently been shown that APC11 alone is sufficient to ubiquitinate APC substrates in the presence of Ubc4 (Gmachl et al, 2000;Leverson et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

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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.

show abstract

Section: Role Of Zn 2؉ Ions In Catalysismentioning

confidence: 99%

Section: Substrate Recognition By Apc and Its Regulation During Cell mentioning

confidence: 99%

Section: Mechanism Of Ubiquitin Transfer Of Apc-catalyzed Reactionsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

View full text Add to dashboard Cite

show abstract

Modes of regulation of ubiquitin-mediated protein degradation

2000

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The ubiquitin-proteasome pathway is responsible for the major portion of specific cellular protein degradation. Ubiquitin-mediated degradation is involved in physiological regulation of many cellular processes, including cell cycle progression, differentiation, and signal transduction. Here, we review the basic mechanisms of the ubiquitin system and the various ways in which ubiquitin-mediated degradation can be modulated by physiological signals.

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Ubiquitin-mediated proteolysis of vertebrate G1- and S-phase regulators

Yew

2001

J. Cell. Physiol.

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Cell-cycle progression in all eukaryotes is driven by cyclin-dependent kinases (CDKs) and their cyclin partners. In vertebrates, the proper and timely duplication of the genome during S-phase relies on the coordinated activities of positive regulators such as CDK±cyclins and E2F, and negative regulators such as CDK inhibitors of the Cip/Kip and INK4 families. Recent and ongoing work indicates that many important regulators of G1-and S-phases are targeted for ubiquitination and subsequent degradation by the 26S proteasome. The proteolysis of key proteins during G1-and S-phases appears to be central for proper custodial regulation of DNA replication and the maintenance of cellular homeostasis in general. This review highlights the current literature regarding ubiquitin-mediated proteolysis of G1-and S-phase regulators and the control of events during the initiation and completion of DNA replication in vertebrates.

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Cdc53/cullin and the essential Hrt1 RING-H2 subunit of SCF define a ubiquitin ligase module that activates the E2 enzyme Cdc34

Cited by 374 publications

References 54 publications

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

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

Modes of regulation of ubiquitin-mediated protein degradation

Ubiquitin-mediated proteolysis of vertebrate G1- and S-phase regulators

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