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

Yew, P. Renée

doi:10.1002/1097-4652(2001)9999:9999<1::aid-jcp1049>3.0.co;2-o

Cited by 91 publications

(59 citation statements)

References 137 publications

(279 reference statements)

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“…In the majority of examined cases, site-specific phosphorylation is required for targeting proteins for proteasomal degradation (Yew, 2001). Our initial observation of a strong correlation between forskolin-induced phosphorylation of cyclin D3 and its instability is in agreement with these findings, and supports the hypothesis that phosphorylation does have an important role in regulation of cyclin D3 stability.…”

Section: Discussionsupporting

confidence: 88%

“…Forskolin promotes cyclin D3 degradation via a proteasome-dependent pathway Many cell-cycle proteins, such as cyclins D1, E and A, are degraded by proteasome-mediated proteolysis (Yew, 2001). Therefore, we wished to determine the involvement of proteasome function in degradation of cyclin D3, and whether proteasomal activity is required for forskolin-mediated increase in cyclin D3 turnover.…”

Section: Forskolin Accelerates Cyclin D3 Turnovermentioning

confidence: 99%

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cAMP-induced degradation of cyclin D3 through association with GSK-3β

Naderi

Gützkow

Låhne

et al. 2004

Journal of Cell Science

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In this study we report a new mechanism whereby cyclic AMP (cAMP) regulates the cell-cycle machinery. We demonstrate that elevation of intracellular levels of cAMP promotes degradation of cyclin D3 in proteasomes, and that this occurs via glycogen synthase kinase-3β (GSK-3β)-mediated phosphorylation of cyclin D3 at Thr-283. Elevation of cAMP did not change the subcellular distribution of either cyclin D3 or GSK-3β. However, cAMP promoted the interaction between cyclin D3 and GSK-3β both in vitro and in vivo, indicating that GSK-3β-mediated phosphorylation of cyclin D3 might require the association between the two proteins. These results demonstrate how cAMP enhances degradation of cyclin D3. Furthermore, we provide evidence for a novel mechanism by which GSK-3β might phosphorylate unprimed substrates in vivo.

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Section: Discussionsupporting

confidence: 88%

Section: Forskolin Accelerates Cyclin D3 Turnovermentioning

confidence: 99%

cAMP-induced degradation of cyclin D3 through association with GSK-3β

Naderi

Gützkow

Låhne

et al. 2004

Journal of Cell Science

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“…UBC encodes a poly-ubiquitin precursor that can conjugate with different residues and lead to various effects within a cell (41). Yew (42) demonstrated that G1-and S-phase events in vertebrates, which were essential for cell proliferation, were specifically mediated by a multitude of regulators associated with ubiquitination, of which UBC was required. Furthermore, Gruber et al (43) reported that cells in IDD lost their ability to proliferate and were subject to senescence.…”

Section: Discussionmentioning

confidence: 99%

Identification of the potential molecular targets for human intervertebral disc degeneration based on bioinformatic methods

Xue

Liu

et al. 2015

International Journal of Molecular Medicine

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Abstract. The present study aimed to explore potential molecular targets and gain further insights into the mechanism of intervertebral disc degeneration (IDD) progression. Microarray datasets of GSE19943, GSE15227 and GSE34095 were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) in 3 IDD specimens compared with 3 controls in GSE34095, DEGs in 7 grade III and 3 grade IV samples compared with 5 grade II samples in GSE19943, and differentially expressed miRNAs in 3 degenerated samples compared with 3 controls in GSE15227 were screened. Grade III-and IV-specific networks were constructed and grade-specific genes were extracted. The network features were analyzed, followed by Gene Ontology (GO) enrichment analysis and pathway enrichment analysis of grade-specific genes and DEGs identified in GSE34095. Furthermore, miRNA-pathway interactions were analyzed using Fisher's exact test. Tumor protein p53 (TP53) was a hub gene in the grade III-specific network and ubiquitin C (UBC) was identified to be a hub gene in the grade IV-specific network. Six significant features were identified by grade-specific network topology analysis. Grade-specific genes and DEGs were involved in different GO terms and pathways. Differentially expressed miRNAs were identified to participate in 35 pathways, among which 6 pathways were significantly enriched by DEGs, including apoptosis. The present study identified that key genes (TP53 and UBC) and miR-129-5p may participate in the mechanism of IDD progression. Thus, they may be potential therapeutic targets for IDD.

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“…Cells were lysed and His-Ubiquitin was isolated using Ni-NTA beads as described in Materials and methods. The presence of HA-CK2b in these isolates was examined by Western blots using anti-HA antibodies Whereas the degradation of mitotic cyclins requires a destruction box, the degradation of G1 cyclins such as cyclin D and cyclin E involves regulatory phosphorylation events (Yew, 2001;Koepp et al, 2001). Phosphorylation of cyclin D by glycogen synthase kinase-3b is involved in triggering degradation of that cyclin while cell cycle dependent autophosphorylation of cyclin E is involved in its degradation (Diehl et al, 1998;Winston et al, 1999).…”

Section: Examination Of the Putative Destruction Box In Ck2bmentioning

confidence: 99%

Phosphorylation regulates the stability of the regulatory CK2β subunit

et al. 2002

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Protein kinase CK2 is a protein serine/threonine kinase that exhibits elevated expression in a number of cancers and displays oncogenic activity in mice. The regulatory CK2b subunit has a central role in assembly of functional tetrameric CK2 complexes where it participates in modulation of catalytic activity and substrate speci®city. Since overexpression of CK2b results in elevated levels of CK2 activity, we investigated the molecular mechanisms that control its degradation since perturbations in these pathways could contribute to elevated CK2 in cancer. In this study, we demonstrate that CK2b is degraded by a proteasome-dependent pathway and that it is ubiquitinated. We have also investigated the role of phosphorylation and a putative destruction box in regulating its stability in cells. Importantly, replacement of three serine residues within the autophosphorylation site of CK2b with glutamic acid residues resulted in a signi®cant decrease in its degradation indicating that autophosphorylation is involved in regulating its stability. Notably, although the autophosphorylation site of CK2b is remarkably conserved between species, this is the ®rst functional role ascribed to this site. Furthermore, based on these results, we speculate that alterations in the phosphorylation or dephosphorylation of the regulatory CK2b subunit could underlie the elevated expression of CK2 that is observed in cancer cells.

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

Cited by 91 publications

References 137 publications

cAMP-induced degradation of cyclin D3 through association with GSK-3β

cAMP-induced degradation of cyclin D3 through association with GSK-3β

Identification of the potential molecular targets for human intervertebral disc degeneration based on bioinformatic methods

Phosphorylation regulates the stability of the regulatory CK2β subunit

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