SUMOylation inhibits FOXM1 activity and delays mitotic transition.

Abstract:

:The forkhead box transcription factor FOXM1 is an essential effector of G2/M-phase transition, mitosis and the DNA damage response. As such, it is frequently deregulated during tumorigenesis. Here we report that FOXM1 is dynamically modified by SUMO1 but not by SUMO2/3 at multiple sites. We show that FOXM1 SUMOylation is enhanced in MCF-7 breast cancer cells in response to treatment with epirubicin and mitotic inhibitors. Mutation of five consensus conjugation motifs yielded a SUMOylation-deficient mutant FOXM1. Conversely, fusion of the E2 ligase Ubc9 to FOXM1 generated an auto-SUMOylating mutant (FOXM1-Ubc9). Analysis of wild-type FOXM1 and mutants revealed that SUMOylation inhibits FOXM1 activity, promotes translocation to the cytoplasm and enhances APC/Cdh1-mediated ubiquitination and degradation. Further, expression of the SUMOylation-deficient mutant enhanced cell proliferation compared with wild-type FOXM1, whereas the FOXM1-Ubc9 fusion protein resulted in persistent cyclin B1 expression and slowed the time from mitotic entry to exit. In summary, our findings suggest that SUMOylation attenuates FOXM1 activity and causes mitotic delay in cytotoxic drug response.

journal_name

Oncogene

journal_title

Oncogene

authors

Myatt SS,Kongsema M,Man CW,Kelly DJ,Gomes AR,Khongkow P,Karunarathna U,Zona S,Langer JK,Dunsby CW,Coombes RC,French PM,Brosens JJ,Lam EW

doi

10.1038/onc.2013.546

subject

Has Abstract

pub_date

2014-08-21 00:00:00

pages

4316-29

issue

34

eissn

0950-9232

issn

1476-5594

pii

onc2013546

journal_volume

33

pub_type

杂志文章

相关文献

ONCOGENE文献大全
  • Crosstalk between NRF2 and HIPK2 shapes cytoprotective responses.

    abstract::Homeodomain interacting protein kinase-2 (HIPK2) is a member of the HIPK family of stress-responsive kinases that modulates cell growth, apoptosis, proliferation and development. HIPK2 has several well-characterised tumour suppressor roles, but recent studies suggest it can also contribute to tumour progression, altho...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2017.221

    authors: Torrente L,Sanchez C,Moreno R,Chowdhry S,Cabello P,Isono K,Koseki H,Honda T,Hayes JD,Dinkova-Kostova AT,de la Vega L

    更新日期:2017-11-02 00:00:00

  • Low expression of pro-apoptotic Bcl-2 family proteins sets the apoptotic threshold in Waldenström macroglobulinemia.

    abstract::Waldenström macroglobulinemia (WM) is a proliferative disorder of IgM-secreting, lymphoplasmacytoid cells that inhabit the lymph nodes and bone marrow. The disease carries a high prevalence of activating mutations in MyD88 (91%) and CXCR4 (28%). Because signaling through these pathways leads to Bcl-xL induction, we ex...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2015.103

    authors: Gaudette BT,Dwivedi B,Chitta KS,Poulain S,Powell D,Vertino P,Leleu X,Lonial S,Chanan-Khan AA,Kowalski J,Boise LH

    更新日期:2016-01-28 00:00:00

  • The MutSβ complex is a modulator of p53-driven tumorigenesis through its functions in both DNA double-strand break repair and mismatch repair.

    abstract::Loss of the DNA mismatch repair (MMR) protein MSH3 leads to the development of a variety of tumors in mice without significantly affecting survival rates, suggesting a modulating role for the MutSβ (MSH2-MSH3) complex in late-onset tumorigenesis. To better study the role of MSH3 in tumor progression, we crossed Msh3(-...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2013.365

    authors: van Oers JM,Edwards Y,Chahwan R,Zhang W,Smith C,Pechuan X,Schaetzlein S,Jin B,Wang Y,Bergman A,Scharff MD,Edelmann W

    更新日期:2014-07-24 00:00:00

  • The mammary pathology of genetically engineered mice: the consensus report and recommendations from the Annapolis meeting.

    abstract::NIH sponsored a meeting of medical and veterinary pathologists with mammary gland expertise in Annapolis in March 1999. Rapid development of mouse mammary models has accentuated the need for definitions of the mammary lesions in genetically engineered mice (GEM) and to assess their usefulness as models of human breast...

    journal_title:Oncogene

    pub_type: 共识发展会议,杂志文章,评审

    doi:10.1038/sj.onc.1203277

    authors: Cardiff RD,Anver MR,Gusterson BA,Hennighausen L,Jensen RA,Merino MJ,Rehm S,Russo J,Tavassoli FA,Wakefield LM,Ward JM,Green JE

    更新日期:2000-02-21 00:00:00

  • Loss of heterozygosity and mutational alterations of the p53 gene in skin tumours of interspecific hybrid mice.

    abstract::Functional alterations or loss of tumor-suppressor genes are an important feature of neoplastic progression in humans. The employment of suitable animal model systems would greatly facilitate the detection and manipulation of such genes. We describe here an experimental approach to this problem based on the analysis o...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Burns PA,Kemp CJ,Gannon JV,Lane DP,Bremner R,Balmain A

    更新日期:1991-12-01 00:00:00

  • Inhibition of endogenous reverse transcriptase antagonizes human tumor growth.

    abstract::Undifferentiated cells and embryos express high levels of endogenous non-telomerase reverse transcriptase (RT) of retroposon/retroviral origin. We previously found that RT inhibitors modulate cell growth and differentiation in several cell lines. We have now sought to establish whether high levels of RT activity are d...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1208562

    authors: Sciamanna I,Landriscina M,Pittoggi C,Quirino M,Mearelli C,Beraldi R,Mattei E,Serafino A,Cassano A,Sinibaldi-Vallebona P,Garaci E,Barone C,Spadafora C

    更新日期:2005-06-02 00:00:00

  • Therapeutic approaches to AIDS-related malignancies.

    abstract::The introduction of highly active antiretroviral therapy (HAART) has changed dramatically the landscape of HIV disease. Deaths from AIDS-related diseases have been reduced by 75% since protease inhibitor therapy and combination antiretroviral therapy came into use in late 1995. While KS is declining, the situation for...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/sj.onc.1206771

    authors: Berretta M,Cinelli R,Martellotta F,Spina M,Vaccher E,Tirelli U

    更新日期:2003-09-29 00:00:00

  • Characterization of transcription factor E2F complexes during muscle and neuronal differentiation.

    abstract::The activities of E2F transcription factors are inhibited by interactions with members of the retinoblastoma (RB) tumor suppressor family, p105RB, p107 and p130. In cycling cells p107 and p130 also interact with heterodimers comprised of Cdk2 and either A or E cyclins. We characterized E2F complexes present in C2C12 a...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Corbeil HB,Whyte P,Branton PE

    更新日期:1995-09-07 00:00:00

  • Isolation of a distinct class of gain-of-function SHP-2 mutants with oncogenic RAS-like transforming activity from solid tumors.

    abstract::SHP-2 protein tyrosine phosphatase plays an important role in activation of the RAS-dependent signaling. Gain-of-function mutations in the PTPN11 gene, which encodes SHP-2, have been found in the leukemia-prone developmental disorder Noonan syndrome as well as sporadic childhood leukemias, indicating that SHP-2 is a b...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1211019

    authors: Miyamoto D,Miyamoto M,Takahashi A,Yomogita Y,Higashi H,Kondo S,Hatakeyama M

    更新日期:2008-06-05 00:00:00

  • RNA silencing of S-phase kinase-interacting protein 2 inhibits proliferation and centrosome amplification in lung cancer cells.

    abstract::The S-phase kinase-associated protein-2 (SKP2) plays a key role in ubiquitin-mediated proteolysis, which results in the progression of cells from a quiescence to proliferative state. SKP2 is overexpressed in a variety of tumors. In this study, we used small interfering RNAs (siRNAs) to inhibit the SKP2 expression in l...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1208459

    authors: Jiang F,Caraway NP,Li R,Katz RL

    更新日期:2005-05-12 00:00:00

  • Phosphorylation of Ets1 regulates the complementation of a CSF-1 receptor impaired in mitogenesis.

    abstract::Ets1, the founder member of the Ets transcription factor family, is involved in a variety of developmental and cellular processes. Previous studies have shown that serine phosphorylation of Ets1 inhibits its DNA binding activity, suggesting that phosphorylation is important in the regulation of Ets1 function. To furth...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Rabault B,Roussel MF,Quang CT,Ghysdael J

    更新日期:1996-08-15 00:00:00

  • 2-Methoxyestradiol induces apoptosis in Ewing sarcoma cells through mitochondrial hydrogen peroxide production.

    abstract::The Ewing sarcoma is the second most common bone tumor in children and young adults. Despite the advances in therapy, the 5-year survival rate for patients with metastatic disease is poor, indicating the need for alternative treatments. Here, we report that 2-methoxy-estradiol (2-Me), a natural estrogen metabolite, in...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1206356

    authors: Djavaheri-Mergny M,Wietzerbin J,Besançon F

    更新日期:2003-05-01 00:00:00

  • Effects of hTERT on metal ion-induced genomic instability.

    abstract::There is currently a great interest in delayed chromosomal and other damaging effects of low-dose exposure to a variety of pollutants which appear collectively to act through induction of stress-response pathways related to oxidative stress and ageing. These have been studied mostly in the radiation field but evidence...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1209399

    authors: Glaviano A,Nayak V,Cabuy E,Baird DM,Yin Z,Newson R,Ladon D,Rubio MA,Slijepcevic P,Lyng F,Mothersill C,Case CP

    更新日期:2006-06-08 00:00:00

  • E2F-3 accumulation is regulated by polypeptide stability.

    abstract::E2F is a complex family of transcription factors which appears to regulate the transcription of genes required for the S phase of the mammalian cell cycle. In the present work, we have examined the mechanisms regulating E2F-3 accumulation in mouse fibroblasts. We have determined that E2F-3 DNA binding activity is rest...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1201633

    authors: Flores AM,Kassatly RF,Cress WD

    更新日期:1998-03-12 00:00:00

  • A variety of tumours induced by the middle T antigen of polyoma virus in a transgenic mouse family.

    abstract::A transgenic mouse family expressing the middle T antigen of polyoma virus under control of the immunoglobulin heavy chain (IgE) enhancer showed the frequent occurrence of carcinomas in various organs, predominantly in females. Most frequently affected were the salivary and thyroid glands, but mammary tumours, liver h...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Rassoulzadegan M,Courtneidge SA,Loubière R,el Baze P,Cuzin F

    更新日期:1990-10-01 00:00:00

  • Differential contributions of ERK and PI3-kinase to the regulation of cyclin D1 expression and to the control of the G1/S transition in mouse embryonic stem cells.

    abstract::Mouse embryonic stem (ES) cells are known to express D-type cyclins at very low levels and these levels increase dramatically during in vitro and in vivo differentiation. Here, we investigate some of the signalling pathways regulating expression of cyclin D1 and progression to S phase, the Ras/Extracellular signal-reg...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1205728

    authors: Jirmanova L,Afanassieff M,Gobert-Gosse S,Markossian S,Savatier P

    更新日期:2002-08-15 00:00:00

  • S100A14 suppresses metastasis of nasopharyngeal carcinoma by inhibition of NF-kB signaling through degradation of IRAK1.

    abstract::Nasopharyngeal carcinoma (NPC) is a unique head and neck cancer with highly aggressive and metastatic potential in which distant metastasis is the main reason for treatment failure. Till present, the underlying molecular mechanisms of NPC metastasis remains poorly understood. Here, we identified S100 calcium-binding p...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-020-1363-8

    authors: Meng DF,Sun R,Liu GY,Peng LX,Zheng LS,Xie P,Lin ST,Mei Y,Qiang YY,Li CZ,Xu L,Peng XS,Hu H,Lang YH,Liu ZJ,Wang MD,Guo LL,Xie DH,Shu DT,Li HF,Luo FF,Niu XT,Huang BJ,Qian CN

    更新日期:2020-07-01 00:00:00

  • Identification of NF-kappa B-regulated genes induced by TNFalpha utilizing expression profiling and RNA interference.

    abstract::Tumor necrosis factor alpha (TNF alpha) is a proinflammatory cytokine with important roles in regulating inflammatory responses as well as cell cycle proliferation and apoptosis. Although TNFalpha stimulates apoptosis, it also activates the transcription factor NF-kappa B, and studies have shown that inhibition of NF-...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1206262

    authors: Zhou A,Scoggin S,Gaynor RB,Williams NS

    更新日期:2003-04-03 00:00:00

  • Overexpression of c-fos in a human pre-B cell acute lymphocytic leukemia derived cell line, SMS-SB.

    abstract::The c-fos proto-oncogene is found to be overexpressed at least 30-fold in SMS-SB, a pre-B leukemic cell line compared to other cell types. No gross alteration of the c-fos gene structure in SMS-SB cells can be detected by karyotypic or Southern analyses. C-fos in SMS-SB cells can still be induced by serum, TPA and the...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Tsai LH,Nanu L,Smith RG,Ozanne B

    更新日期:1991-01-01 00:00:00

  • Mouse model for lung tumorigenesis through Cre/lox controlled sporadic activation of the K-Ras oncogene.

    abstract::The onset of human lung cancer occurs through sequential mutations in oncogenes and tumor suppressor genes. Mutations in K-Ras play a prominent role in human non-small cell lung cancer. We have developed a mouse lung tumor model in which K-Ras can be sporadically activated through Cre-lox mediated somatic recombinatio...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1204837

    authors: Meuwissen R,Linn SC,van der Valk M,Mooi WJ,Berns A

    更新日期:2001-10-04 00:00:00

  • Molecular mechanisms underlying interferon-alpha-induced G0/G1 arrest: CKI-mediated regulation of G1 Cdk-complexes and activation of pocket proteins.

    abstract::One prominent effect of IFNs is their cell growth-inhibitory activity. The mechanism behind this inhibition of proliferation is still not fully understood. In this study, the effect of IFN-alpha treatment on cell cycle progression has been analysed in three lymphoid cell lines, Daudi, U-266 and H9. Examination of the ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1202609

    authors: Sangfelt O,Erickson S,Castro J,Heiden T,Gustafsson A,Einhorn S,Grandér D

    更新日期:1999-05-06 00:00:00

  • Ligand-associated ERBB2/3 activation confers acquired resistance to FGFR inhibition in FGFR3-dependent cancer cells.

    abstract::Somatic alterations of fibroblast growth factor receptors (FGFRs) have been described in a wide range of malignancies. A number of anti-FGFR therapies are currently under investigation in clinical trials for subjects with FGFR gene amplifications, mutations and translocations. Here, we develop cell line models of acqu...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2014.161

    authors: Wang J,Mikse O,Liao RG,Li Y,Tan L,Janne PA,Gray NS,Wong KK,Hammerman PS

    更新日期:2015-04-23 00:00:00

  • Polymorphisms in the p53 pathway.

    abstract::The p53 tumor suppressor gene continues to be distinguished as the most frequently mutated gene in human cancer; this gene can be found mutated in up to 50% of human tumors of diverse histological type. It is generally accepted that the ability of p53 to induce either growth arrest or programmed cell death in response...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/sj.onc.1209367

    authors: Pietsch EC,Humbey O,Murphy ME

    更新日期:2006-03-13 00:00:00

  • Betaglycan drives the mesenchymal stromal cell osteogenic program and prostate cancer-induced osteogenesis.

    abstract::Bone metastatic prostate cancer provokes extensive osteogenesis by driving the recruitment and osteoblastic differentiation of mesenchymal stromal cells (MSCs). The resulting lesions greatly contribute to patient morbidity and mortality, underscoring the need for defining how prostate metastases subvert the MSC-osteob...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-019-0913-4

    authors: Cook LM,Frieling JS,Nerlakanti N,McGuire JJ,Stewart PA,Burger KL,Cleveland JL,Lynch CC

    更新日期:2019-10-01 00:00:00

  • 2-deoxyglucose-induced toxicity is regulated by Bcl-2 family members and is enhanced by antagonizing Bcl-2 in lymphoma cell lines.

    abstract::Targeting altered cancer cell metabolism with the glycolysis inhibitor, 2-deoxyglucose (2DG), is a viable therapeutic strategy, but the effects of 2DG on lymphoma cells and the mechanism of action are unknown. Five T-cell lymphoma lines and two B-cell lymphoma lines were shown to be highly sensitive to 2DG. Examinatio...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2011.454

    authors: Zagorodna O,Martin SM,Rutkowski DT,Kuwana T,Spitz DR,Knudson CM

    更新日期:2012-05-31 00:00:00

  • LOT1 is a growth suppressor gene down-regulated by the epidermal growth factor receptor ligands and encodes a nuclear zinc-finger protein.

    abstract::We previously reported cloning the rLot1 gene, and its human homolog (hLOT1), through analysis of differential gene expression in normal and malignant rat ovarian surface epithelial cells. Both human and rat ovarian carcinoma cell lines exhibited lost or decreased expression of this gene. Interestingly, the LOT1 gene ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1203067

    authors: Abdollahi A,Bao R,Hamilton TC

    更新日期:1999-11-11 00:00:00

  • OTX1 expression in breast cancer is regulated by p53.

    abstract::The p53 transcription factor has a critical role in cell stress response and in tumor suppression. Wild-type p53 protein is a growth modulator and its inactivation is a critical event in malignant transformation. It has been recently demonstrated that wild-type p53 has developmental and differentiation functions. Inde...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2011.31

    authors: Terrinoni A,Pagani IS,Zucchi I,Chiaravalli AM,Serra V,Rovera F,Sirchia S,Dionigi G,Miozzo M,Frattini A,Ferrari A,Capella C,Pasquali F,Curto FL,Albertini A,Melino G,Porta G

    更新日期:2011-07-07 00:00:00

  • Regulation of mitotic exit by the RNF8 ubiquitin ligase.

    abstract::RNF8 is a ubiquitin ligase with a FHA domain near its N terminus, and a RING-finger domain at its C terminus, through which it recruits several ubiquitin-conjugating enzymes. In metazoans, only the mitotic checkpoint regulator CHFR shares this domain architecture. Here we show that RNF8 is a nuclear protein that follo...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1210782

    authors: Plans V,Guerra-Rebollo M,Thomson TM

    更新日期:2008-02-28 00:00:00

  • Silencing effect of CpG island hypermethylation and histone modifications on O6-methylguanine-DNA methyltransferase (MGMT) gene expression in human cancer.

    abstract::O6-methylguanine-DNA methyltransferase (MGMT) repairs the cytotoxic and mutagenic O6-alkylguanine produced by alkylating agents such as chemotherapeutic agents and mutagens. Recent studies have shown that in a subset of tumors, MGMT expression is inversely linked to hypermethylation of the CpG island in the promoter r...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1207183

    authors: Nakagawachi T,Soejima H,Urano T,Zhao W,Higashimoto K,Satoh Y,Matsukura S,Kudo S,Kitajima Y,Harada H,Furukawa K,Matsuzaki H,Emi M,Nakabeppu Y,Miyazaki K,Sekiguchi M,Mukai T

    更新日期:2003-12-04 00:00:00

  • Activation of Stat5 by platelet-derived growth factor (PDGF) is dependent on phosphorylation sites in PDGF beta-receptor juxtamembrane and kinase insert domains.

    abstract::Signal transducers and activators of transcription (Stats) are known to transduce signals from the cell surface to the nucleus in cytokine receptor signaling. We examined the capacity of platelet-derived growth factor (PDGF) receptor to interact with and activate Stat molecules. Activation of the PDGF beta-receptor le...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1201555

    authors: Valgeirsdóttir S,Paukku K,Silvennoinen O,Heldin CH,Claesson-Welsh L

    更新日期:1998-01-29 00:00:00