Combinatorial control in ubiquitin-dependent proteolysis: don't Skp the F-box hypothesis

Patton, E. Elizabeth; Willems, Andrew; Tyers, Mike

doi:10.1016/s0168-9525(98)01473-5

Cited by 480 publications

(441 citation statements)

References 62 publications

Supporting

Mentioning

430

Contrasting

Unclassified

Order By: Relevance

“…Yaron et al (1998) employed this elegant cellfree system along with highly sensitive protein puri®cation and sequence determination technology to molecularly identify the component of the E3 activity responsible for recognition of phospho-IkB. This protein, named E3RS IkB , turned out to be a member of the F-box/WD-repeat family (reviewed in Patton et al, 1998). Interestingly, other members of this family, which contain an F-box and one or two WD or leucine-rich repeats, are essential components of E3 activities involved in regulated protein degradation (Bai et al, 1996;Feldman et al, 1997;Skowyra et al, 1997).…”

Section: Regulation Of Ikb Turnovermentioning

confidence: 99%

“…For instance, two members of this group, Cdc4 and Grr1, that share 30% similarity with E3RS IkB , mediate the binding of their cognate E3 complexes to phosphorylated substrates, Sic1 and Cln2, respectively. E3RS IkB , Cdc4 and Grr1, recognize phosphoamino acids that are embedded within a speci®c sequence through their WD repeat domain (Patton et al, 1998;Yaron et al, 1998). The F box domain, on the other hand, is responsible for binding to Skp1, which in turn binds to members of the Cullin family, such as Cdc53 or Cul1 (Feldman et al, 1997;Skowyra et al, 1997).…”

Section: Regulation Of Ikb Turnovermentioning

confidence: 99%

“…The F box domain, on the other hand, is responsible for binding to Skp1, which in turn binds to members of the Cullin family, such as Cdc53 or Cul1 (Feldman et al, 1997;Skowyra et al, 1997). The Cullin subunit appears to mediate recruitment of E2-ubiquitin onto the phosphorylated substrate (Patton et al, 1998).…”

Section: Regulation Of Ikb Turnovermentioning

confidence: 99%

See 2 more Smart Citations

How NF-κB is activated: the role of the IκB kinase (IKK) complex

1999

View full text Add to dashboard Cite

Rel/NF-kB transcription factors are primarily regulated by association with inhibitor IkB proteins. Thus, in most cells NF-kB exists in the cytoplasm in an inactive complex bound to IkB. Most agents that activate NF-kB do so through a common pathway based on phosphorylation-induced, proteasome-mediated degradation of IkB. The key regulatory step in this pathway involves activation of a high molecular weight IkB kinase (IKK) complex, whose catalysis is generally carried out by a heterodimeric kinase consisting of IKKa and IKKb subunits. This review describes the identi®cation of proteins in the IKK complex, and the regulation and physiological functions of IKK.

show abstract

Section: Regulation Of Ikb Turnovermentioning

confidence: 99%

Section: Regulation Of Ikb Turnovermentioning

confidence: 99%

See 1 more Smart Citation

How NF-κB is activated: the role of the IκB kinase (IKK) complex

1999

View full text Add to dashboard Cite

show abstract

“…Furthermore, the programmed breakdown of Pds1p/Cut2p (anaphase inhibitor), cohesin, Ctf13p (kinetochore component), geminin (inhibitor of DNA replication), and Ase1p, in addition to mitotic cyclin B, occurs in the progression of mitosis. A recent interesting finding is that the ubiquitinylation The proteasome ᭧ Blackwell Science Limited of these cell-cycle factors, involving G1/S transition and the progression of mitosis, is catalysed by a large multisubunit Ub-ligase named SCF (Skp1-Cdc53 or cullins-F-box protein complex) and cyclosome/APC (anaphase-promoting complex), respectively (reviewed in Hershko 1997;Hoyt 1997;Patton et al 1998). Intriguingly, two APC regulators, Cdc20p/fizzy and Cdc5p (Polo-kinase), are also degraded by the APCdependent ubiqutinylation pathway (Shirayama et al 1998).…”

Section: Biological Roles Of the Ubiquitinylationproteasome Directed mentioning

confidence: 99%

The proteasome: a protein‐destroying machine

Tanaka

Chiba

1998

Genes to Cells

View full text Add to dashboard Cite

Most cellular proteins are targeted for degradation by the proteasome, a eukaryotic ATPdependent protease, after they have been covalently attached to ubiquitin (Ub) in the form of a poly Ub chain functioning as a degradation signal. The proteasome is an unusually large multisubunit proteolytic complex, consisting of a central catalytic machine (called the 20S proteasome) and two terminal regulatory subcomplexes, termed PA700 or PA28, that are attached to both ends of the central portion in opposite orientations, to form enzymatically active proteasomes. The large assembled proteasome acts as a protein-destroying machine responsible for the selective breakdown of numerous ubiquitinylated cellular proteins and certain nonubiquitinylated proteins. To date, proteolysis mediated by the Ub-proteasome pathway has been shown to be involved in a wide variety of biologically important processes, such as the cell cycle, apoptosis, metabolism, signal transduction, immune response and protein quality control, implying that it functions as a previously unrecognized regulatory system for determining the final fate of protein factors involved in these biological reactions.

show abstract

“…Yeast and mammalian cells encode several di erent F-box proteins. In yeast at least three SCF complexes exist SCF Grr1 , SCF Cdc4 and SCF Met30 where the F-box protein encoded by Grr1, Cdc4 or Met30 respectively provides substrate speci®city to the ligase complex (Skowyra et al, 1997;Patton et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Inhibitory effect of p21 in MCF-7 cells is overcome by its coordinated stabilization with D-type cyclins

1999

View full text Add to dashboard Cite

Coordinated accumulation of cyclin D1 and D3 is observed in 15% of primary breast cancers and in the breast cancer cell line MCF-7 this simultaneous overexpression is due to a defect in their ubiquitin-mediated proteolysis. The F-box protein Skp2 is a component of an SCF ubiquitin ligase complex and can associate with cyclin D1 and the cdk inhibitor p21 (Zhong-Kang et al., 1998). We extend this observation and show that cyclin D3 can also associate with Skp2 suggesting that cyclins D1, D3 and p21 may share the same SCF complex. In agreement with this hypothesis we report here that in primary breast cancers and in MCF-7 cells where cyclins D1 and D3 are elevated the level of p21 is also elevated. Further, we demonstrate that the turnover of p21 protein is reduced in MCF-7 cells. We show that p21 is active as a cdk inhibitor in this cell line but that the presence of elevated levels of cyclin D3 titrates p21 away from cyclin D1-cdk4/6 complexes and cdk2 complexes resulting in increased kinase activities. Our results suggest that a defect in the SCF complex may occur in 15 ± 20% of breast cancers and that the resulting coordinated elevation of cyclins D1 and D3 overcomes the inhibition of cell cycle progression by p21. We propose that in the context of cyclins D1 and D3 overexpression, p21 may promote cell cycle progression.

show abstract

Combinatorial control in ubiquitin-dependent proteolysis: don't Skp the F-box hypothesis

Cited by 480 publications

References 62 publications

How NF-κB is activated: the role of the IκB kinase (IKK) complex

How NF-κB is activated: the role of the IκB kinase (IKK) complex

The proteasome: a protein‐destroying machine

Inhibitory effect of p21 in MCF-7 cells is overcome by its coordinated stabilization with D-type cyclins

Contact Info

Product

Resources

About