Genomes and Genes
e2f1 transcription factor
Summary: An E2F transcription factor that interacts directly with RETINOBLASTOMA PROTEIN and CYCLIN A and activates GENETIC TRANSCRIPTION required for CELL CYCLE entry and DNA synthesis. E2F1 is involved in DNA REPAIR and APOPTOSIS.
- Zencak D, Schouwey K, Chen D, Ekstrom P, Tanger E, Bremner R, et al. Retinal degeneration depends on Bmi1 function and reactivation of cell cycle proteins. Proc Natl Acad Sci U S A. 2013;110:E593-601 pubmed publisher..These data reveal that Bmi1 controls the cell cycle-related death process, highlighting this pathway as a promising therapeutic target for neuroprotection in retinal dystrophies...
- Li Y, Zhang D, Ren Q, Ye F, Zhao X, Daniels G, et al. Regulation of a novel androgen receptor target gene, the cyclin B1 gene, through androgen-dependent E2F family member switching. Mol Cell Biol. 2012;32:2454-66 pubmed publisher..Thus, we identified a novel mechanism for E2F factors in the regulation of cell cycle gene expression and cell cycle progression under the control of AR signaling. ..
- Pützer B, Engelmann D. E2F1 apoptosis counterattacked: evil strikes back. Trends Mol Med. 2013;19:89-98 pubmed publisher..These mechanisms explain the paradox of high E2F1 expression in advanced tumors, highlight potential loopholes for cancers to escape from conventional treatment, and imply novel therapeutic strategies. ..
- Ji W, Zhang W, Xiao W. E2F-1 directly regulates thrombospondin 1 expression. PLoS ONE. 2010;5:e13442 pubmed publisher..Taken together, the results demonstrate that TSP1 is a novel target for E2F1, which might imply that E2F-1 can affect angiogenesis by modulating TSP1 expression. ..
- Budhavarapu V, White E, Mahanic C, Chen L, Lin F, Lin W. Regulation of E2F1 by APC/C Cdh1 via K11 linkage-specific ubiquitin chain formation. Cell Cycle. 2012;11:2030-8 pubmed publisher..The data suggest that DNA damage signaling processes do not inhibit APC/C (Cdh1) to ubiquitinate E2F1. Instead, they block the proteasomal degradation of Ub-K11-linked E2F1, and therefore lead to its accumulation. ..
- Cho E, Zheng S, Munro S, Liu G, Carr S, Moehlenbrink J, et al. Arginine methylation controls growth regulation by E2F-1. EMBO J. 2012;31:1785-97 pubmed publisher..Our results establish that arginine methylation regulates the biological activity of E2F-1 activity, and raise the possibility that arginine methylation contributes to tumourigenesis by influencing the E2F pathway. ..
- Bueno M, Gómez de Cedrón M, Laresgoiti U, Fernandez Piqueras J, Zubiaga A, Malumbres M. Multiple E2F-induced microRNAs prevent replicative stress in response to mitogenic signaling. Mol Cell Biol. 2010;30:2983-95 pubmed publisher..Given the known function of E2F of inducing other oncogenic miRNAs, control of miRNAs by E2F is likely to play multiple roles in cell proliferation and in proliferative diseases such as cancer. ..
- Docquier A, Harmand P, Fritsch S, Chanrion M, Darbon J, Cavailles V. The transcriptional coregulator RIP140 represses E2F1 activity and discriminates breast cancer subtypes. Clin Cancer Res. 2010;16:2959-70 pubmed publisher..This study shows that RIP140 is a regulator of the E2F pathway, which discriminates luminal- and basal-like tumors, emphasizing the importance of these regulations for a clinical cancer phenotype. ..
- Chang J, Hsu H, Ni H, Chuang C, Hsiung C, Huang T, et al. Distinct epigenetic domains separated by a CTCF bound insulator between the tandem genes, BLU and RASSF1A. PLoS ONE. 2010;5:e12847 pubmed publisher..3 gene cluster region. ..
- Carcagno A, Marazita M, Ogara M, Ceruti J, Sonzogni S, Scassa M, et al. E2F1-mediated upregulation of p19INK4d determines its periodic expression during cell cycle and regulates cellular proliferation. PLoS ONE. 2011;6:e21938 pubmed publisher..This regulatory mechanism constitutes a new negative feedback loop that terminates the G1 phase proliferative signal, contributing to the proper coordination of the cell cycle and provides an additional mechanism to limit E2F activity. ..
- Warg L, Oakes J, Burton R, Neidermyer A, Rutledge H, Groshong S, et al. The role of the E2F1 transcription factor in the innate immune response to systemic LPS. Am J Physiol Lung Cell Mol Physiol. 2012;303:L391-400 pubmed publisher..These miRNAs represent novel regulators of the innate immune response. In summary, we used transcriptional and miRNA profiling to characterize the response of E2F1-deficient mice to systemic LPS. ..
- Wu Z, Zheng S, Li Z, Tan J, Yu Q. E2F1 suppresses Wnt/?-catenin activity through transactivation of ?-catenin interacting protein ICAT. Oncogene. 2011;30:3979-84 pubmed publisher..This study provides a mechanistic insight into the antagonistic interaction between E2F1 and ?-catenin signaling. ..
- Sáez Ayala M, Fernández Pérez M, Montenegro M, Sánchez del Campo L, Chazarra S, Piñero Madrona A, et al. Melanoma coordinates general and cell-specific mechanisms to promote methotrexate resistance. Exp Cell Res. 2012;318:1146-59 pubmed publisher..Under these conditions, melanoma cells are protected from apoptosis by arresting their cell cycle in S phase. Excess of dTTP could also inhibit E2F1-mediated apoptosis in melanoma cells. ..
- Engelmann D, Pützer B. The dark side of E2F1: in transit beyond apoptosis. Cancer Res. 2012;72:571-5 pubmed publisher..This raises the perspective of new drug targets at late-stage cancer. ..
- Ingram L, Munro S, Coutts A, La Thangue N. E2F-1 regulation by an unusual DNA damage-responsive DP partner subunit. Cell Death Differ. 2011;18:122-32 pubmed publisher..Our results define a new pathway, which acts independently of pRb and through a biochemically distinct mechanism, involved in negative regulation of E2F-1 activity. ..
- Helgason G, O Prey J, Ryan K. Oncogene-induced sensitization to chemotherapy-induced death requires induction as well as deregulation of E2F1. Cancer Res. 2010;70:4074-80 pubmed publisher..Due to the frequent deregulation of E2F1 in human cancer, these studies reveal potentially important insights into E2F1-mediated chemotherapeutic responses that may aid the development of novel targeted therapies for malignant disease. ..
- Lin R, Lin Y, Yu A. miR-149* induces apoptosis by inhibiting Akt1 and E2F1 in human cancer cells. Mol Carcinog. 2010;49:719-27 pubmed publisher..Our findings not only provided the first evidence that Akt1 is a direct target of miRNA but also demonstrated that miR-149* is a pro-apoptotic miRNA by repressing the expression of Akt1 and E2F1. ..
- Real S, Meo Evoli N, Espada L, Tauler A. E2F1 regulates cellular growth by mTORC1 signaling. PLoS ONE. 2011;6:e16163 pubmed publisher..From these studies, E2F1 emerges as a key protein that integrates cell division and growth, both of which are essential for cell proliferation. ..
- Malhotra S, Lapointe J, Salari K, Higgins J, Ferrari M, Montgomery K, et al. A tri-marker proliferation index predicts biochemical recurrence after surgery for prostate cancer. PLoS ONE. 2011;6:e20293 pubmed publisher..Our findings highlight the potential value of a multi-gene signature-based diagnostic, and define a tri-marker proliferation index with possible utility for improved prognostication and treatment stratification in prostate cancer. ..
- Wenzel P, Chong J, Sáenz Robles M, Ferrey A, Hagan J, Gomez Y, et al. Cell proliferation in the absence of E2F1-3. Dev Biol. 2011;351:35-45 pubmed publisher..Together, these data implicate E2F1-3 in mediating transcriptional repression by Rb during cell cycle exit and point to a critical role for their repressive functions in cell survival. ..
- Yang G, Zhang R, Chen X, Mu Y, Ai J, Shi C, et al. MiR-106a inhibits glioma cell growth by targeting E2F1 independent of p53 status. J Mol Med (Berl). 2011;89:1037-50 pubmed publisher..Further investigations will focus on the therapeutic use of miR-106a-mediated antitumor effects in glioma. ..
- Yang M, Wu S, Jia J, May W. JAZ mediates G1 cell cycle arrest by interacting with and inhibiting E2F1. Cell Cycle. 2011;10:2390-9 pubmed
- Blanchet E, Annicotte J, Lagarrigue S, Aguilar V, Clapé C, Chavey C, et al. E2F transcription factor-1 regulates oxidative metabolism. Nat Cell Biol. 2011;13:1146-52 pubmed publisher..Thus, E2F1 represents a metabolic switch from oxidative to glycolytic metabolism that responds to stressful conditions. ..
- Höög G, Zarrizi R, von Stedingk K, Jönsson K, Alvarado Kristensson M. Nuclear localization of ?-tubulin affects E2F transcriptional activity and S-phase progression. FASEB J. 2011;25:3815-27 pubmed publisher..Thus, we report a novel mechanism regulating the activity of E2Fs, which can help explain how these proteins affect cell cycle progression in mammalian cells. ..
- Davis R, Pillai S, Lawrence N, Sebti S, Chellappan S. TNF-?-mediated proliferation of vascular smooth muscle cells involves Raf-1-mediated inactivation of Rb and transcription of E2F1-regulated genes. Cell Cycle. 2012;11:109-18 pubmed publisher..These results suggest that inhibiting the Rb-Raf-1 interaction is a potential avenue to prevent VSMC proliferation associated with atherosclerosis. ..
- Biswas A, Johnson D. Transcriptional and nontranscriptional functions of E2F1 in response to DNA damage. Cancer Res. 2012;72:13-7 pubmed publisher..This review summarizes recent progress made in understanding the role of E2F1 in the DNA damage response, including transcription-independent activities that facilitate DNA repair in the context of chromatin. ..
- Shi L, Su B. Identification and functional characterization of a primate-specific E2F1 binding motif regulating MCPH1 expression. FEBS J. 2012;279:491-503 pubmed publisher..Nucleotide sequence data are available in the GenBank database (http://www.ncbi.nlm.nih.gov/genbank/) under accession numbers JN573214, JN573215 and JN573216...
- Wang C, Chien K, Wang C, Liu H, Cheng C, Chang Y, et al. Quantitative proteomics reveals regulation of karyopherin subunit alpha-2 (KPNA2) and its potential novel cargo proteins in nonsmall cell lung cancer. Mol Cell Proteomics. 2012;11:1105-22 pubmed publisher..Our results collectively demonstrate the utility of quantitative proteomic approaches and provide a fundamental platform to further explore the biological roles of KPNA2 in nonsmall cell lung cancer. ..
- He S, Yang S, Deng G, Liu M, Zhu H, Zhang W, et al. Aurora kinase A induces miR-17-92 cluster through regulation of E2F1 transcription factor. Cell Mol Life Sci. 2010;67:2069-76 pubmed publisher..These data reveal a novel link between AURKA and microRNAs via the regulation of E2F1, providing new clues for understanding the role of AURKA in tumorigenesis. ..
- Ernst A, Campos B, Meier J, Devens F, Liesenberg F, Wolter M, et al. De-repression of CTGF via the miR-17-92 cluster upon differentiation of human glioblastoma spheroid cultures. Oncogene. 2010;29:3411-22 pubmed publisher..Our results suggest that miR-17-92 and its target CTGF mediate effects of differentiation-promoting treatment on glioblastoma cells through multiple regulatory pathways. ..
- Xu H, Ren W, Zou L, Wang Y, Jin R, Zhou G. Direct repression of the human IRF-3 promoter by E2F1. Immunogenetics. 2011;63:189-96 pubmed publisher..Chromatin immunoprecipitation assays demonstrate that E2F1 interacts with the IRF-3 promoter in vivo. These results suggest that E2F1 negatively regulates IRF-3 transcription through binding to the E2F consensus binding site. ..
- Kachhap S, Rosmus N, Collis S, Kortenhorst M, Wissing M, Hedayati M, et al. Downregulation of homologous recombination DNA repair genes by HDAC inhibition in prostate cancer is mediated through the E2F1 transcription factor. PLoS ONE. 2010;5:e11208 pubmed publisher..that several DNA repair genes are downregulated by HDAC inhibition and provide a mechanism involving the E2F1 transcription factor in the process...
- Tammali R, Saxena A, Srivastava S, Ramana K. Aldose reductase regulates vascular smooth muscle cell proliferation by modulating G1/S phase transition of cell cycle. Endocrinology. 2010;151:2140-50 pubmed publisher..Thus, inhibition of AR may be a useful therapeutic approach in preventing vascular complications. ..
- Tin A, Sundar S, Tran K, Park A, Poindexter K, Firestone G. Antiproliferative effects of artemisinin on human breast cancer cells requires the downregulated expression of the E2F1 transcription factor and loss of E2F1-target cell cycle genes. Anticancer Drugs. 2012;23:370-9 pubmed publisher..and protein levels of the CDK2 and CDK4 cyclin-dependent kinases, cyclin E, cyclin D1, and the E2F1 transcription factor. Analysis of CDK2 promoter-luciferase reporter constructs showed that the artemisinin ablation of CDK2 ..
- Guo X, Guo L, Ji J, Zhang J, Zhang J, Chen X, et al. miRNA-331-3p directly targets E2F1 and induces growth arrest in human gastric cancer. Biochem Biophys Res Commun. 2010;398:1-6 pubmed publisher..We concluded that miR-331-3p is a potential tumor suppressor in gastric cancer. Restoring miR-331-3p in gastric cancer cells revealed potential application in gastric cancer therapy. ..
- Yeo H, Beh T, Quek J, Koh G, Chan K, Lee D. Integrated transcriptome and binding sites analysis implicates E2F in the regulation of self-renewal in human pluripotent stem cells. PLoS ONE. 2011;6:e27231 pubmed publisher..In addition, we proposed a core self-renewal module of regulatory interplay between E2F and, WNT and FGF pathways in these cells. Thus, we conclude that E2F plays a significant role in influencing the self-renewal capabilities of hPSCs. ..
- Lizé M, Klimke A, Dobbelstein M. MicroRNA-449 in cell fate determination. Cell Cycle. 2011;10:2874-82 pubmed..MiR-449 helps to ensure proper cell function but also to avoid cancer, marking a close link between cell differentiation and tumor suppression. ..
- Kontaki H, Talianidis I. Lysine methylation regulates E2F1-induced cell death. Mol Cell. 2010;39:152-60 pubmed publisher..The findings illustrate that the function of methyltransferases can have opposing biological outcomes depending on the specificity of transcription factor targets. ..
- Wichmann A, Uyetake L, Su T. E2F1 and E2F2 have opposite effects on radiation-induced p53-independent apoptosis in Drosophila. Dev Biol. 2010;346:80-9 pubmed publisher..We conclude that p53-dependent and p53-independent apoptoses show differential reliance on E2F activity in Drosophila. ..
- Dar A, Majid S, De Semir D, Nosrati M, Bezrookove V, Kashani Sabet M. miRNA-205 suppresses melanoma cell proliferation and induces senescence via regulation of E2F1 protein. J Biol Chem. 2011;286:16606-14 pubmed publisher..E2F1 overexpression in miR-205-expressing cells partially reversed the effects on melanoma cell growth and senescence. These results demonstrate a novel role for miR-205 as a tumor suppressor in melanoma. ..
- Gehrke S, Imai Y, SOKOL N, Lu B. Pathogenic LRRK2 negatively regulates microRNA-mediated translational repression. Nature. 2010;466:637-41 pubmed publisher..Our results implicate deregulated synthesis of E2F1/DP caused by the miRNA pathway impairment as a key event in LRRK2 pathogenesis and suggest novel miRNA-based therapeutic strategies. ..
- Gomez Gutierrez J, Garcia Garcia A, Hao H, Rao X, Montes de Oca Luna R, Zhou H, et al. Adenovirus-mediated expression of truncated E2F-1 suppresses tumor growth in vitro and in vivo. Cancer. 2010;116:4420-32 pubmed publisher..The current results indicated that AdTet-E2Ftr3 is a novel anticancer agent that has significant therapeutic activity in vitro and in vivo. ..
- Peart M, Poyurovsky M, Kass E, Urist M, Verschuren E, Summers M, et al. APC/C(Cdc20) targets E2F1 for degradation in prometaphase. Cell Cycle. 2010;9:3956-64 pubmed..These data suggest that APC/C(Cdc20) specifically targets E2F1 for degradation in early mitosis and reveal a novel mechanism for limiting free E2F1 levels in cells, failure of which may compromise cell survival and/or homeostasis. ..
- Guo R, Chen J, Zhu F, Biswas A, Berton T, Mitchell D, et al. E2F1 localizes to sites of UV-induced DNA damage to enhance nucleotide excision repair. J Biol Chem. 2010;285:19308-15 pubmed publisherThe E2F1 transcription factor is a well known regulator of cell proliferation and apoptosis, but its role in the DNA damage response is less clear...
- Sharma A, Yeow W, Ertel A, Coleman I, Clegg N, Thangavel C, et al. The retinoblastoma tumor suppressor controls androgen signaling and human prostate cancer progression. J Clin Invest. 2010;120:4478-92 pubmed publisher..Together, these data reveal what we believe to be a new paradigm for RB function in controlling prostate tumor progression and lethal tumor phenotypes. ..
- Cartier J, Berthelet J, Marivin A, Gemble S, Edmond V, Plenchette S, et al. Cellular inhibitor of apoptosis protein-1 (cIAP1) can regulate E2F1 transcription factor-mediated control of cyclin transcription. J Biol Chem. 2011;286:26406-17 pubmed publisher..Here, we show that the N-terminal part of cIAP1 directly interacts with the DNA binding domain of the E2F1 transcription factor. cIAP1 dramatically increases the transcriptional activity of E2F1 on synthetic and CCNE promoters...
- Xie Q, Bai Y, Wu J, Sun Y, Wang Y, Zhang Y, et al. Methylation-mediated regulation of E2F1 in DNA damage-induced cell death. J Recept Signal Transduct Res. 2011;31:139-46 pubmed publisher..The identification of the methylation/demethylation of E2F1 by Set9/LSD1 suggests that E2F1 is dynamically regulated by epigenetic enzymes in response to DNA damage. ..
- Bertin Ciftci J, Barre B, Le Pen J, Maillet L, Couriaud C, Juin P, et al. pRb/E2F-1-mediated caspase-dependent induction of Noxa amplifies the apoptotic effects of the Bcl-2/Bcl-xL inhibitor ABT-737. Cell Death Differ. 2013;20:755-64 pubmed publisher..Thus, caspases contribute to trigger the mitochondrial apoptotic pathway by coupling Bcl-2/Bcl-xL inhibition to that of Mcl-1, via the pRb/E2F-1-dependent induction of Noxa. ..
- Zhai J, Yin X, Lai Y, Hou X, Cai J, Hao X, et al. Sorafenib enhances the chemotherapeutic efficacy of S-1 against hepatocellular carcinoma through downregulation of transcription factor E2F-1. Cancer Chemother Pharmacol. 2013;71:1255-64 pubmed publisher..05). Sorafenib enhanced therapeutic efficacy of 5-FU/S-1 against HCC through downregulation of E2F-1 and TS expressions. Sorafenib combined with S-1 might represent as valuable therapeutic regimen against HCC. ..
- Ofir M, Hacohen D, Ginsberg D. MiR-15 and miR-16 are direct transcriptional targets of E2F1 that limit E2F-induced proliferation by targeting cyclin E. Mol Cancer Res. 2011;9:440-7 pubmed publisher..Furthermore, inhibition of both miR-15 and miR-16 enhances E2F1-induced G(1)/S transition. In summary, our data identify the miR-15 and miR-16 families as novel transcriptional targets of E2F, which, in turn, modulates E2F activity. ..
- Alla V, Kowtharapu B, Engelmann D, Emmrich S, Schmitz U, Steder M, et al. E2F1 confers anticancer drug resistance by targeting ABC transporter family members and Bcl-2 via the p73/DNp73-miR-205 circuitry. Cell Cycle. 2012;11:3067-78 pubmed publisher..These results define the E2F1-p73/DNp73-miR-205 axis as a crucial mechanism for chemoresistance and, thus, as a target for metastasis prevention...
- Li C, Nyman J, Braithwaite A, Eccles M. PAX8 promotes tumor cell growth by transcriptionally regulating E2F1 and stabilizing RB protein. Oncogene. 2011;30:4824-34 pubmed publisher..Therefore, our results suggest that, in cancer, frequent and persistent expression of PAX8 is required for cell growth control through transcriptional activation of E2F1 expression and upregulation of the RB-E2F1 pathway. ..
- Tategu M, Nakagawa H, Sasaki K, Yamauchi R, Sekimachi S, Suita Y, et al. Transcriptional regulation of human polo-like kinases and early mitotic inhibitor. J Genet Genomics. 2008;35:215-24 pubmed publisher..Collectively, these results indicate that E2F can integrate G(1)/S and G(2)/M to oscillate the cell cycle by regulating mitotic genes PLK and Emi, leading to determination of the cell fate. ..
- Pulikkan J, Dengler V, Peramangalam P, Peer Zada A, Muller Tidow C, Bohlander S, et al. Cell-cycle regulator E2F1 and microRNA-223 comprise an autoregulatory negative feedback loop in acute myeloid leukemia. Blood. 2010;115:1768-78 pubmed publisher..Our study supports a molecular network involving miR-223, C/EBPalpha, and E2F1 as major components of the granulocyte differentiation program, which is deregulated in AML. ..
- Molina Privado I, Rodríguez Martínez M, Rebollo P, Martin Perez D, Artiga M, Menarguez J, et al. E2F1 expression is deregulated and plays an oncogenic role in sporadic Burkitt's lymphoma. Cancer Res. 2009;69:4052-8 pubmed publisher..Because E2F1 is not needed for cell proliferation of normal cells, our results reveal E2F1 as a promising therapeutic target for sBL. ..
- Shaw J, Yurkova N, Zhang T, Gang H, Aguilar F, Weidman D, et al. Antagonism of E2F-1 regulated Bnip3 transcription by NF-kappaB is essential for basal cell survival. Proc Natl Acad Sci U S A. 2008;105:20734-9 pubmed publisher..Our data may explain more fundamentally how cells, by selectively inhibiting E2F-1-dependent death gene transcription, avert apoptosis down-stream of the retinoblastoma/E2F-1 cell cycle pathway. ..