Cyclin E2: a novel CDK2 partner in the late G1 and S phases of the mammalian cell cycle

Lauper, Nathalie; Beck, Andreas; Cariou, Sandrine; Richman, Larry; Hofmann, Kay; Reith, Walter; Slingerland, Joyce M.; Amati, Bruno

doi:10.1038/sj.onc.1202477

Cited by 131 publications

(118 citation statements)

References 32 publications

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“…Cdk2 and Cdk3 activities increase rapidly in mid to late G1 phase and peak close to the G1 to S transition (reviewed in [43]). Both Cdk2 and Cdk3 form complexes with cyclins A and E as well as with more recently identified cyclins A1 [44] and E2 [45]. Furthermore, both Cdk2 and Cdk3 are inhibited by p21 Cip1 and p27 Kip1 CKIs [46].…”

Section: Ink4 Family Of Ckimentioning

confidence: 84%

Regulation of the G1 phase of the mammalian cell cycle

2000

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In any multi-cellular organism, the balance between cell division and cell death maintains a constant cell number. Both cell division cycle and cell death are highly regulated events. Whether the cell will proceed through the cycle or not, depends upon whether the conditions required at the checkpoints during the cycle are fulfilled. In higher eucaryotic cells, such as mammalian cells, signals that arrest the cycle usually act at a G1 checkpoint. Cells that pass this restriction point are committed to complete the cycle. Regulation of the G1 phase of the cell cycle is extremely complex and involves many different families of proteins such as retinoblastoma family, cyclin dependent kinases, cyclins, and cyclin kinase inhibitors.Key words: Cell cycle, cyclin dependent kinase, cyclin, cyclin kinase inhibitor. Retinoblastoma family of proteinsThe retinoblastoma family consists of three members: pRb, p107, and p130, that are all important in the cell cycle regulation. Studies from knockout mice showed that pRb null mutation is embryonically lethal, while p107 or p130 knockout mice have no known * Corresponding author.Tel: (301) 517-0355; Fax: (301) 517-0344; E-mail: scottd@usa.redcross.org Abbreviations used in this paper: pRb,retinoblastoma protein; CDK, cyclin dependent kinase; CKI, cyclin kinase inhibitor; IgM, immunoglobulin M; BCR, B cell receptor; BHFR, dihydrofolate reductase; TGF-β, transforming growyh factorβ.

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Section: Ink4 Family Of Ckimentioning

confidence: 84%

Regulation of the G1 phase of the mammalian cell cycle

2000

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“…Our study is the first to date that analyzed the effect of CCNE2 mRNA on RFI in primary breast cancer patients. CCNE2 is encoded by a different gene than CCNE1 and was only recently characterized by Lauper et al 28 Although CCNE1 and CCNE2 proteins share 47% similarity and are both implicated in G1/S progression of the cell cycle, it has been speculated that CCNE2 could not be simply redundant with CCNE1, but might regulate distinct rate-limiting pathways in G1/S control. For example, here we showed that expression levels of CCNE1 but not CCNE2 were associated with the expression of the proliferation marker Ki67.…”

Section: Discussionmentioning

confidence: 99%

Impact of cyclins E, neutrophil elastase and proteinase 3 expression levels on clinical outcome in primary breast cancer patients

Desmedt

Ouriaghli

Durbecq

et al. 2006

Intl Journal of Cancer

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Uncontrolled cell proliferation is one of the hallmarks of cancer and the transition from the G1 to S phase is the most commonly reported cell cycle abnormality in tumors. It has been shown that the oncogenic activity of G1 cyclin E (CCNE) can be amplified by generating hyperactive low molecular weight forms (LMW) through elastase-mediated proteolytic processing. Neutrophil elastase (NE) and proteinase 3 (PR3) are 2 proteases that are aberrantly expressed in breast cancer cells and seem to be involved in cell proliferation. In this study, we evaluated the effect of the expression of these 2 proteases in addition to 2 potential intracellular targets of NE (CCNE1 and CCNE2) on clinical outcome in a population of 205 primary breast cancer patients. By univariate analysis, CCNE1, CCNE2, estrogen receptor and grade significantly predicted relapse free interval (RFI). NE and PR3 did not achieve statistical significance. In a multivariate analysis, elevated CCNE2 [hazard ratio (HR) 2.10, p 5 0.008] predicted shorter RFI. In subgroup analyses of the tamoxifen-only treated patients, high CCNE1 levels predicted treatment resistance, while high levels of CCNE2 were associated with poor RFI in untreated patients. Investigation of the relationship between CCNE1, CCNE2 and NE did not show any impact on RFI. To conclude, this study was the first to evaluate these markers at the mRNA level by RT-PCR in a series of primary breast cancer patients, and our results confirmed the impact of high CCNE levels on clinical outcome in systemically untreated and of CCNE1 in tamoxifen-only treated early breast cancer patients. ' 2006 Wiley-Liss, Inc.Key words: breast cancer; elastase; proteinase 3; cyclin E; mRNA Uncontrolled cell proliferation is one of the hallmarks of cancer and the transition from the G1 to S phase is the most commonly reported cell cycle abnormality in tumors. 1 Cyclin E (CCNE), a G1 cyclin which is essential for S-phase entry, has a profound role in oncogenesis, 2,3 and its overexpression has been repeatedly linked with poor patient outcome in breast cancer (reviewed in Ref. 4) and with endocrine therapy failure. 5 Recent studies identified low molecular weight isoforms (LMW) of CCNE, generated specifically in tumors by elastase-mediated proteolytic processing, 6 which were shown to be hyperactive compared to full-length CCNE and associated with poor clinical outcome in stage I to III breast cancer patients. 7 Recently, it has been shown that high levels of neutrophil elastase (NE) protein in breast cancer tissue extracts were associated with poor clinical outcome and with endocrine treatment failure in patients with advanced breast cancer disease. 8,9 This prognostic value was supposedly linked with the essential role of NE in the degradation of the extracellular matrix and the metastasis process. 10,11 But since NE may be aberrantly produced by breast cancer cells themselves and because NE has been implicated in the intracellular cleavage of CCNE in its LMW forms, its prognostic value may be linked to its property ...

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“…5,[8][9][10] Deletion or mutation of the F-box protein Fbw7, part of the Skp1-Cul1-Rbx1 ubiquitin ligase complex (SCF Fbw7 ) that targets cyclin E for proteosomal degradation, 11,12 is also highly correlated with chromosome instability. 13 Although cyclins E1 and E2 are often coordinately regulated, share strong sequence similarity in functional important regions, including the cyclin box and centrosomal localization sequence, 14 and appear to be functionally redundant during murine development, 1,[15][16][17][18][19] there is accumulating evidence that, like many cyclins, they have distinct roles under some circumstances. 20 For example, during liver regeneration, cyclin E1 promotes endoreduplication, while cyclin E2 suppresses it.…”

Section: Introductionmentioning

confidence: 99%