2003
DOI: 10.1074/jbc.m205768200
|View full text |Cite
|
Sign up to set email alerts
|

Dictyostelium Differentiation-inducing Factor-3 Activates Glycogen Synthase Kinase-3β and Degrades Cyclin D1 in Mammalian Cells

Abstract: In search of chemical substances applicable for the treatment of cancer and other proliferative disorders, we studied the signal transduction of Dictyostelium differentiation-inducing factors (DIFs) in mammalian cells mainly using HeLa cells. Although DIF-1 and DIF-3 both strongly inhibited cell proliferation by inducing G 0 /G 1 arrest, DIF-3 was more effective than DIF-1. DIF-3 suppressed cyclin D1 expression at both mRNA and protein levels, whereas the overexpression of cyclin D1 overrode DIF-3-induced cell… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
1
1

Citation Types

7
92
2

Year Published

2006
2006
2017
2017

Publication Types

Select...
6
2
1

Relationship

3
6

Authors

Journals

citations
Cited by 101 publications
(101 citation statements)
references
References 28 publications
7
92
2
Order By: Relevance
“…This result suggests that DIFs inhibited cyclin D1 mRNA expression via the inhibition of β-catenin / TCF-dependent transcription activity. On the other hand, we also found that the activated GSK-3β translocated to the nucleus and phosphorylated cyclin D1 on Thr 286 to trigger the degradation of cyclin D1 by an ubiquitin-dependent mechanism (28,30,31). Correlated with the above observations, DIFs induced G0 / G1 cell cycle arrest, which was rescued by the overexpression of cyclin D1 (28), suggesting that DIFs were likely to induce cell cycle arrest by reducing the expression of cyclin D1.…”
supporting
confidence: 54%
“…This result suggests that DIFs inhibited cyclin D1 mRNA expression via the inhibition of β-catenin / TCF-dependent transcription activity. On the other hand, we also found that the activated GSK-3β translocated to the nucleus and phosphorylated cyclin D1 on Thr 286 to trigger the degradation of cyclin D1 by an ubiquitin-dependent mechanism (28,30,31). Correlated with the above observations, DIFs induced G0 / G1 cell cycle arrest, which was rescued by the overexpression of cyclin D1 (28), suggesting that DIFs were likely to induce cell cycle arrest by reducing the expression of cyclin D1.…”
supporting
confidence: 54%
“…Therefore, activation of GSK-3β is expected to cause a reduction in both protein and mRNA levels of cyclin D1 through independent pathways. Indeed, DIFs induced phosphorylation of the Thr 286 residue of cyclin D1 and β-catenin degradation, resulting in the reduction of cyclin D1 in the protein and mRNA levels (82,84,85). We also found that DIFs reduced the activity of a TCF reporter plasmid and a reporter gene driven by the human cyclin D1 promoter (83).…”
Section: -4 Potential Drug Targetsmentioning
confidence: 63%
“…Differentiation-inducing factors (DIF) are effector molecules that have a phenol unit and can alter cell chemistry. DIF-1 and DIF-3 have been reported to inhibit b-catenin by activating GSK3-b [10].…”
Section: Targeting the Wnt-b-catenin Pathwaymentioning
confidence: 99%