2005
DOI: 10.1038/sj.onc.1208326
|View full text |Cite
|
Sign up to set email alerts
|

Phosphorylation of cyclin D1 at Thr 286 during S phase leads to its proteasomal degradation and allows efficient DNA synthesis

Abstract: Continuing proliferation requires regulation of cyclin D1 levels in each cell cycle phase. Growth factors stimulate high levels during G2 phase, which commits the cell to continue through G1 phase with sufficient cyclin D1 to initiate DNA synthesis. Upon entry into S phase, however, cyclin D1 levels rapidly decline. Our goal is to understand the mechanism and importance of this S-phase suppression. Here, we demonstrate that cyclin D1 levels decline during S phase due to reduced protein stability, without alter… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
1
1

Citation Types

3
100
0

Year Published

2006
2006
2016
2016

Publication Types

Select...
9

Relationship

3
6

Authors

Journals

citations
Cited by 78 publications
(103 citation statements)
references
References 27 publications
3
100
0
Order By: Relevance
“…This technique involves fluorescent staining and accurate quantitation on a cell-by-cell basis, and has been useful in cell cycle studies of cyclin D1 and p27 expression in asynchronous cultures. [24][25][26]33,34 We utilized this single cell based analysis here to critically relate the timing of CDK2 phosphorylation to the initiation of DNA synthesis. First, however, it was necessary to identify an antibody able to recognize CDK2 phosphorylated on Thr-160 in individual cells.…”
Section: Resultsmentioning
confidence: 99%
“…This technique involves fluorescent staining and accurate quantitation on a cell-by-cell basis, and has been useful in cell cycle studies of cyclin D1 and p27 expression in asynchronous cultures. [24][25][26]33,34 We utilized this single cell based analysis here to critically relate the timing of CDK2 phosphorylation to the initiation of DNA synthesis. First, however, it was necessary to identify an antibody able to recognize CDK2 phosphorylated on Thr-160 in individual cells.…”
Section: Resultsmentioning
confidence: 99%
“…What could be the role of this down-regulation in hepatocarcinogenesis? High levels of cyclin D1 in the cell nucleus during the S phase inhibit DNA synthesis; efficient cell proliferation requires glycogen synthase kinase 3hÀdependent phosphorylation of cyclin D1 following its export from the nucleus and subsequent degradation (51). However, the oncogenic alternatively spliced isoform of cyclin D1 lacks the phosphorylation site and remains nuclear (32), showing that at some stage, cancer cells can overcome the inhibition of DNA synthesis by cyclin D1.…”
Section: Discussionmentioning
confidence: 99%
“…Cyclin D1 induction is a rate-limiting event during cell-cycle entry from quiescence into the G 1 phase (19). For DNA synthesis to occur during S-phase, cyclin D1 proteins should be downregulated (37). Parthenolide treatment at 10 mmol/L concentrations for 3 and 6 hours transiently decreased cyclin D1 protein levels (Fig.…”
Section: Parthenolide Induces S-phase Arrest In Nonpromoted Cells Andmentioning
confidence: 99%