Cdk2 associates with MAP Kinase in vivo and its nuclear translocation is dependent on MAP Kinase activation in IL-2-dependent Kit 225 T lymphocytes

Blanchard, Dominique; Mouhamad, Shahul; Auffredou, Marie Thérèse; Pesty, Arlette; Bertoglio, Jacques; Leca, Gérald; Vázquez, Aimé

doi:10.1038/sj.onc.1203761

Cited by 33 publications

(25 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, it has been shown that the nucleocytoplasmic translocation of Cdk2 is under the control of p42/p44 MAPKs in fibroblasts (43,44). Cytoplasmic mislocalization of Cdk2 has also been reported to be a key event in vitamin D-mediated growth inhibition of prostate cancer cells (45) and in irradiation-induced apoptosis in mouse mesangial cells (46).…”

Section: Discussionmentioning

confidence: 99%

p38 mitogen-activated protein kinase contributes to cell cycle regulation by cAMP in FRTL-5 thyroid cells

Correze¹,

Blondeau²,

Pomérance³

2005

eur j endocrinol

View full text Add to dashboard Cite

Objective: Thyrotropin activates the cAMP pathway in thyroid cells, and stimulates cell cycle progression in cooperation with insulin or insulin-like growth factor-I. Because p38 mitogen-activated protein kinases (p38 MAPKs) were stimulated by cAMP in the FRTL-5 rat thyroid cell line, we investigated (i) the effect of the specific inhibition of p38 MAPKs on FRTL-5 cell proliferation and (ii) the mechanism of action of p38 MAPKs on cell cycle control, by studying the expression and/or the activity of several cell cycle regulatory proteins in FRTL-5 cells. Methods: DNA synthesis was monitored by incorporation of [ 3 H]thymidine into DNA and the cell cycle distribution was assessed by fluorescence-activated cell sorter analysis. Expression of cell cycle regulatory proteins was determined by Western blot analysis. Cyclin-dependent kinase 2 (Cdk2) activity associated to cyclin E was immunoprecipitated and was measured by an in vitro kinase assay. Results: SB203580, an inhibitor of a and b isoforms of p38 MAPKs, but not its inactive analog SB202474, inhibited DNA synthesis and the G1-S transition induced by forskolin plus insulin. SB203580 inhibited specifically p38 MAPK activity but not other kinase activities such as Akt and p70-S6 kinase. Treatment of FRTL-5 cells with SB203580 decreased total and cyclin E-associated Cdk2 kinase activity stimulated with forskolin and insulin. However, inhibition of p38 MAPKs by SB203580 was without effect on total cyclin E and Cdk2 levels. The decrease in Cdk2 kinase activity caused by SB203580 treatment was not due to an increased expression of p21Cip1 or p27 Kip1 inhibitory proteins. In addition, SB203580 affected neither Cdc25A phosphatase expression nor Cdk2 Tyr-15 phosphorylation. Inhibition of p38 MAPKs decreased Cdk2-cyclin E activation by regulating the subcellular localization of Cdk2 and its phosphorylation on Thr-160. Conclusions: These results indicate that p38 MAPK activity is involved in the regulation of cell cycle progression in FRTL-5 thyroid cells, at least in part by increasing nuclear Cdk2 activity. 153 123-133 European Journal of Endocrinology

show abstract

Section: Discussionmentioning

confidence: 99%

p38 mitogen-activated protein kinase contributes to cell cycle regulation by cAMP in FRTL-5 thyroid cells

Correze¹,

Blondeau²,

Pomérance³

2005

eur j endocrinol

View full text Add to dashboard Cite

show abstract

“…Reports suggest a possible role of the ERK signaling pathway in the regulation of Cdk2 translocation (52,53,56). The decrease in nuclear Cdk2 following 1,25-(OH) 2 D 3 treatment may occur via decreased nuclear import and/or increased nuclear export of Cdk2.…”

Section: Vitamin D Causes Cdk2 Mislocalization and Stabilizes P27mentioning

confidence: 99%

Vitamin D Inhibits G1 to S Progression in LNCaP Prostate Cancer Cells through p27Kip1 Stabilization and Cdk2 Mislocalization to the Cytoplasm

Yang

Burnstein

2003

Journal of Biological Chemistry

133

View full text Add to dashboard Cite

1,25-(OH)2Kip1 levels, inhibition of cyclin-dependent kinase 2 (Cdk2) activity, hypophosphorylation of retinoblastoma protein, and accumulation of cells in G 1 . In this study, we investigated the mechanism whereby 1,25-(OH) 2 D 3 increases p27 levels. 1,25-(OH) 2 D 3 had no effect on p27 mRNA levels or on the regulation of a 3.5-kb fragment of the p27 promoter. Our previous studies established that the initial growth inhibition of LNCaP and its androgen-independent derivative LNCaP-104R1 by 1,25-(OH) 2 D 3 correlates with an increase in the levels of the cyclin-dependent kinase inhibitors (CKIs) p21 WAF1,CIP1 and p27 Kip1 , a profound decrease in cyclin-dependent kinase 2 (Cdk2) activity, hypophosphorylation of pRb, and accumulation of cells in the G 1 phase of the cell cycle (12, 13). 1,25-(OH) 2 D 3 also decreased transcriptional activity of the E2F transcription factor family, which regulates the expression of genes necessary for S phase entry (12).The CKI p27 appears to play a more central role than p21 in growth inhibition mediated by 1,25-(OH) 2 D 3 and its analogs (13,14). In several prostate cancer cell lines, 1,25-(OH) 2 D 3 treatment results in persistent up-regulation of p27, whereas p21 is only induced transiently (12-14). In addition, 1,25-(OH) 2 D 3 -mediated growth inhibition of the androgen-independent LNCaP-derivative LNCaP-104R1 cells occurs without induction of p21 (13).Loss of p27 expression correlates with prostate cancer recurrence, a more aggressive phenotype, and decreased patient prognosis and survival (15)(16)(17)(18)(19)(20)(21)(22). Reduced p27 protein, however, is not the result of p27 gene mutations, which are quite rare in cancers (23-25). Activation of oncogenic signaling pathways ultimately results in accelerated p27 proteolysis and decreased p27 levels (26 -29). Understanding the mechanisms whereby p27 levels are regulated may yield new targets for potential anticancer agents. Because of the emerging role of p27 in controlling prostate cancer growth, we further investigated the mechanism of 1,25-(OH) 2 D 3 regulation of this CKI in LNCaP cells.p27 is an important regulator of the G 1 to S phase transition. p27 binds and inhibits cyclin E/Cdk2 and thereby negatively regulates S phase entry. To traverse G 1 , cellular p27 levels must decrease. A major mechanism to achieve this regulation involves ubiquitin-dependent p27 proteolysis (30,31). Two rate-limiting steps for this process include phosphorylation at Thr 187 by Cdk2 and recognition of Thr 187 -phospho-p27 by the SCF skp2 ubiquitination system (17,(32)(33)(34)(35)(36). Recent studies have revealed a novel pathway for p27 degradation at the G 0 /early G 1 phase of the cell cycle that is independent of Thr 187 phos- Cdk2, cyclin-dependent kinase 2; UTR, untranslated region; PBS, phosphate-buffered saline; CAK, Cdk-activating kinase.

show abstract

“…Cdk2 activation is dependent on its localization in the nucleus. Blanchard et al reported that nuclear translocation of Cdk2 and the resulting G 1 /S transtion of IL-2 dependent Kit 225 T cell is directly associated with the physical interaction of Cdk2 with MAPK and dependent on MAPK activity [17].…”

Section: Erk Pathwaymentioning

confidence: 99%

MAPK signal pathways in the regulation of cell proliferation in mammalian cells

2002

View full text Add to dashboard Cite

MAPK families play an important role in complex cellular programs like proliferation, differentiation, development, transformation, and apoptosis. At least three MAPK families have been characterized: extracellular signal-regulated kinase (ERK), Jun kinase (JNK/SAPK) and p38 MAPK. The above effects are fulfilled by regulation of cell cycle engine and other cell proliferation related proteins. In this paper we discussed their functions and cooperation with other signal pathways in regulation of cell proliferation.

show abstract

Cdk2 associates with MAP Kinase in vivo and its nuclear translocation is dependent on MAP Kinase activation in IL-2-dependent Kit 225 T lymphocytes

Cited by 33 publications

References 54 publications

p38 mitogen-activated protein kinase contributes to cell cycle regulation by cAMP in FRTL-5 thyroid cells

p38 mitogen-activated protein kinase contributes to cell cycle regulation by cAMP in FRTL-5 thyroid cells

Vitamin D Inhibits G1 to S Progression in LNCaP Prostate Cancer Cells through p27Kip1 Stabilization and Cdk2 Mislocalization to the Cytoplasm

MAPK signal pathways in the regulation of cell proliferation in mammalian cells

Contact Info

Product

Resources

About