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| '''E2F''' is a group of genes that codifies a family of [[transcription factor]]s (TF) in higher [[eukaryotes]]. Three of them are activators: E2F1, 2 and E2F3a. Six others act as suppressors: E2F3b, E2F4-8. All of them are involved in the [[cell cycle]] regulation and synthesis of DNA in [[mammal]]ian cells. E2Fs as TFs bind to the TTTCCCGC (or slight variations of this sequence) consensus [[binding site]] in the target [[promoter (biology)|promoter]] sequence.
| | New Condominium is an upcoming combined improvement located in Yishun Central, Northern Region of Singapore. This development is strategically situated next to Northpoint Buying Centre and reverse of Yishun Train Station. New Condominium is a ninety nine years leasehold mission that has a site area of roughly 442,397 sq. toes. Upon completion it's going to comprise of an estimated 890 residential items and 359,084 sq. ft of commercial space.<br><br>Evaluation now by visiting the brand new condominium pages on our site, each displaying comprehensive details and the newest info of each new launch. You can too contact us directly to receive fast & correct answers to all of your questions with top of the line service. The nearby private housing developments are mainly low-rise landed property giving extra privacy and exclusivity to the new development. The virtually unspoil environment is what differentiates this growth from the encompassing ones (VII) Park Connector With solely 118 beautiful units, Belgravia Villas at Ang Mo Kio is the most anticipated freehold cluster home launch in 2013! Commonwealth Towers Condo beside Queenstown MRT Station Compass Point (Approx 1.6KM) Colleges Nearby Riverbank Fernvale Apartment<br><br>With Singapore conserving its greenery and with the town sky view being the attraction to many, it is no wonder that increasingly condos are being developed on the island. Many future investors are putting more value on items with a view than these with out one. Thus, this can be one of the reasons too as to why your unit of alternative is either with a view or without. I'm not encouraging you to ‘leap' into a property buy, however to perform a little research and make a judgement name. The Crest Rental at Prince Charles Crest, Wing Tai upcomingcondo Launch now open for expression of curiosity. Calculation of using CPF funds for Property Less than 60 years however more than 30 years New Apartment in 2013 September New Condo 2013 August New Condo Waterfront @ Faber COULD<br><br>Fitness enthusiast and nature lovers will find the nearby Bishan Ang Mo Kio park, Macritchie reservoir, nature reserve, golf course, stadium, swimming advanced, sports corridor a plus plus point as a resident of Sky Vue rental. Famend instructional institution are also within close proximity of Sky Vue rental. There is a choice for everybody at Sky Vue apartment, with unit mixture of 1 bed room, 2 bed room, 2 bed room suite, 3 bedroom as well as penthouses. View Sky Vue Condo floor plan Sky Vue Condominium - Undertaking Description Bartley Ridge is a brand new rental situated within a singapore new launch; [http://www.pro-ps.ru/wiki/doku.php/the_phrase_on_the_road_a_poet_for_a_son mouse click the next web site], residential enclave along Mount Vernon Street, with Bartley MRT station nearby. Learn More → The Sorrento is an Exciting New Freehold Condominium providing the Ultimate Luxurious dwelling within the West. Read Extra →<br><br>Now that you have all these to consider, it's a good suggestion to search for for real estate brokers that may aid you in making the right action of investing on the proper property once you are ready. A dependable agent will just be sure you have the proper funds for a new rental launch investing. With out figuring out the precise quantity of how a lot you're keen to spend, you can be quick in the long run since it's a must to guantee that the budget also covers the upkeep bills. These expenses will steadily enhance yr by year and if you are investing without a monetary plan, the dream of getting your individual non-public residential unit will never be a reality.<br><br>Ocean Membership Resorts in Turks & Caicos is offering as much as 25 % low cost on rooms this Cyber Monday. Book online and use promo code "CYBER" to receive 20 % off all room categories and receive a $200 lodge credit score for 5 or extra night time stays for travel between January three and February 7, 2014. Or get 25 percent off juniors, one, two and three bedrooms and receive a $200 lodge credit for 5 or more night stays for travel between May 1 and December 18, 2014. Can't be combined with any further low cost, including EBB. The Cyber Monday sale is 24 hours solely.<br><br>This high-rise luxurious condominium can also be a really brief walk from Queenstown MRT station, which gives handy travel to all parts of Singapore on the MRT strains island huge. Even throughout the property itself, daily needs are nicely taken care of, including for recreation and leisure. I still bear in mind the detrimental voices saying property prices will drop when I first began out in actual property in 2010. Trying on the chart now, I'm sure your reply can be – ‘Yes, I'd probably buy in 2006 or 2010.' Now the correct time to purchase a New Launch Condo? 28RC Suites is a Freehold Blended Growth situated at 28 Race Course Lane in prime district 8 of Singapore. Located within walking distance to Farrer Read Extra Continuereading "Trilive at Kovan Preview Launch Soon"<br><br>Vero Seaside Resort & Spa and Kimpton's Surfcomber in South Seashore and Miami are offering two deals. The first is 15 p.c off the perfect obtainable price while you stay for 2 nights. The second deal is 20 p.c off one of the best out there charge if you keep for 3 nights. Company reserving at Surfcomber will receive a free appetizer at the Social Membership while visitors reserving on the Vero receive a free appetizer on the Cobalt. This off is obtainable for travel by means of Christmas 2013. To make reservations at Surfcomber, call 800-994-62013 or visit the lodge's website For reservations at Vero Beach, name 1-866-602-8376 or go to the resort's website Ensure that to use the code CYBER for each deals. |
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| ==E2F family==
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| Schematic diagram of the [[peptide sequence|amino acid sequence]]s of E2F family members ([[N-terminus]] to the left, [[C-terminus]] to the right) highlighting the relative locations of functional [[protein domain|domains]] within each member:
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| {| class="wikitable"
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| |-
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| ! Family members
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| ! Legend
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| |-
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| | [[Image:E2F family member.png|400px]]
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| * '''cyc A''' - [[Cyclin A]] binding domain
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| * '''DNA''' - DNA-binding domain
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| * '''DP1,2''' - domain for dimerization with [[TFDP1|DP1]], [[TFDP2|2]]
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| * '''TA''' - transcriptional activation domain
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| * '''PB''' - pocket protein binding domain
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| |}
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| ==Genes==
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| Homo sapiens [http://www.ncbi.nlm.nih.gov/nuccore/NM_005225 E2F1 mRNA] or
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| [http://www.ncbi.nlm.nih.gov/protein/12669911 E2F1 protein] sequences from [[National Center for Biotechnology Information|NCBI]] protein and nucleotide database.
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| ==Structure==
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| [[X-ray crystallography|X-ray crystallographic]] analysis has shown that the E2F family of transcription factors has a [[protein_structure#Tertiary_structure|fold]] similar to the [[winged-helix transcription factors|winged-helix]] [[DNA-binding domain|DNA-binding motif]].<ref name="pmid10090723">{{cite journal | author = Zheng N, Fraenkel E, Pabo CO, Pavletich NP | title = Structural basis of DNA recognition by the heterodimeric cell cycle transcription factor E2F-DP | journal = Genes Dev. | volume = 13 | issue = 6 | pages = 666–74 | year = 1999 | pmid = 10090723 | doi = 10.1101/gad.13.6.666 | url = | pmc = 316551 }}</ref>
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| ==Role in the cell cycle==
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| [[Image:Signal transduction pathways.svg|300px|thumb|right|Overview of signal transduction pathways involved in [[apoptosis]].]]
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| E2F family members play a major role during the G1/S transition in mammalian and plant [[cell cycle]] (see [http://www.genome.jp/dbget-bin/show_pathway?hsa04110+1869 KEGG cell cycle pathway]). [[DNA microarray]] analysis reveals unique sets of target promoters among E2F family members suggesting that each protein has a unique role in the cell cycle.<ref name="ReferenceA">{{cite journal | doi=10.1016/S1097-2765(00)00071-X
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| |title= E2F4 and E2F5 Play an Essential Role in Pocket Protein–Mediated G1 Control |year=2000 |last1=Gaubatz |first1=S.F. |last2=Lindeman |first2=G.J. |last3=Ishida |first3=S. |last4=Jakoi |first4=L. |last5=Nevins|first5=J.R. |last6=Livingston|first6=D.M. |last7=Rempel|first7=R.E. |journal=Molecular Cell |volume=6 |pages=729–735 | issue=3 | pmid=11030352 }}</ref> Among E2F transcriptional targets are [[cyclin]]s, [[Cyclin-dependent kinase|cdk]]s, checkpoints regulators, [[DNA repair]] and replication proteins. Nonetheless, there is a great deal of redundancy among the family members. Mouse embryos lacking E2F1, E2F2, and one of the E2F3 isoforms, can develop normally when either E2F3a or E2F3b, is expressed.<ref>{{cite journal | doi=10.1038/nature07066|title= Mouse development with a single E2F activator |year=2008 |last1=Tsai |first1=S. |last2=Opavsky |first2=R. |last3=Sharma |first3=N. |last4=Wu |first4=L. |last5=Naidu|first5=S. |last6=Nolan|first6=E. |last7=Feria-Arias|first7=E. |last8=Timmers|first8=C. |last9=Opavska|first9=J. | journal=Nature |volume=454 |pages=1137–1141 | issue=7208 | pmid=18594513}}</ref>
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| The E2F family is generally split by function into two groups: transcription activators and repressors. Activators such as E2F1, E2F2, E2F3a promote and help carryout the cell cycle, while repressors inhibit the cell cycle. Yet, both sets of E2F have similar domains. E2F1-6 have DP1,2 heterodimerization domain which allows them to bind to DP1 or DP2, proteins distantly related to E2F. Binding with DP1,2 provides a second DNA binding site, increasing E2F binding stability.<ref>{{cite journal | doi= 10.1104/pp.106.077990|title= Interplay between Arabidopsis Activating Factors E2Fb and E2Fa in Cell Cycle Progression and Development |year=2006|last1=Sozzani |first1=R. |last2=Maggio |first2=C. |last3=Varotto |first3=S. |last4=Canova |first4=S. |last5=Bergounioux|first5=C. |last6=Albani|first6=D. |last7=Cella|first7=F.| journal=Plant Physiology |volume=140 |pages=1355–1366 | issue= 4 | pmid= 16514015 | pmc= 1435807}}</ref> Most E2F have a [[pocket protein family|pocket protein]] binding domain. Pocket proteins such as [[Retinoblastoma protein|pRB]] and related proteins p107 and p130, can bind to E2F when hypophosphorylated. In activators, E2F binding with pRB has been shown to mask the transactivation domain responsible for transcription activation.<ref>{{cite journal | doi= 10.1074/jbc.M501410200 |title= Cloning and Characterization of Mouse E2F8, a Novel Mammalian E2F Family Member Capable of Blocking Cellular Proliferation |year=2005|last1=Maiti |first1=B. |last2=Li |first2=J. |last3=Bruin |first3=A.D. |last4=Gordon |first4=F. |last5=Timmers|first5=C. |last6=Opavsky|first6=R. |last7=Patil|first7=K. |last8=Tuttle|first8=J. |last9=Cleghorn|first9=W. | journal= The Journal of Biological Chemistry |volume=280 |pages=18211–18220 | issue= 18 | pmid= 15722552}}</ref> In repressors E2F4 and E2F5, pocket protein binding (more often p107 and p130 than pRB) mediates recruitment of repression complexes to silence target genes.<ref>{{cite journal | doi= 10.1038/nrc2696|title= Emerging roles of E2Fs in cancer: an exit from cell cycle control |year=2009|last1=Chen |first1=H. |last2=Tsai |first2=S. |last3=Leone |first3=G. | journal= Nature Reviews Cancer |volume=9 |pages=785–797 | issue= 11 | pmid= 19851314 }}</ref> E2F6, E2F7, and E2F8 do not have pocket protein binding sites and their mechanism for gene silencing is unclear. Cdk4(6)/cyclin D and cdk2/cyclin E phosphorylate pRB and related pocket proteins allowing them to disassociate from E2F. Activator E2F proteins can then transcribe S phase promoting genes. In REF52 cells, overexpression of activator E2F1 is able to push quiescent cells into S phase.<ref>{{cite journal |title= Expression of transcription factor E2F1 induces quiescent cells to enter S phase |year=1993 |last1=Johnson |first1=G. |last2=Schwarz |first2=J.K. |last3=Cress |first3=W.D. |last4=Nevins |first4=J.R. |journal=Nature |volume=365 |pages=349–352 |doi= 10.1038/365349a0 |pmid= 8377827 |issue= 6444 }}</ref> While repressors E2F4 and 5 do not alter cell proliferation, they mediate G1 arrest.<ref name="ReferenceA"/>
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| E2F activator levels are cyclic, with maximal expression during G1/S. In contrast, E2F repressors stay constant, especially since they are often expressed in quiescent cells. Specifically, E2F5 is only expressed in terminally differentiated cells in mice.<ref name="ReferenceA"/> The balance between repressor and activator E2F regulate cell cycle progression. When activator E2F family proteins are knocked out, repressors become active to inhibit E2F target genes.<ref>{{cite journal | doi= 10.1128/MCB.02147-06
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| |title= E2f1, E2f2, and E2f3 Control E2F Target Expression and Cellular Proliferation via a p53-Dependent Negative Feedback Loop |year=2007 |last1=Timmers |first1=C. |last2=Sharma |first2=N. |last3=Wu |first3=L. |last4=Wu |first4=J. |last5=Orringer|first5=D. |last6=Trikha|first6=P. |last7=Saavedra|first7=G. |last8=Leone |journal=Molecular and Cellular Biology |volume=27 |pages=65–78 | first8= P. | last9= Saavedra | first9= H. I. | pmid= 17167174 | issue= 1 | pmc= 1800646}}</ref>
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| ==E2F/pRb complexes==
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| The [[Retinoblastoma protein|Rb tumor suppressor protein]] (pRb) binds to the E2F1 transcription factor preventing it from interacting with the cell's transcription machinery. In the absence of pRb, E2F1 (along with its binding partner DP1) mediates the trans-activation of E2F1 target genes that facilitate the G1/S transition and S-phase. E2F target genes encode proteins involved in DNA replication (for example [[DNA polymerase]], [[thymidine kinase]], [[dihydrofolate reductase]] and [[cdc6]]), and chromosomal replication (replication origin-binding protein HsOrc1 and [[MCM5]]). When cells are not proliferating, E2F DNA binding sites contribute to transcriptional repression. In vivo footprinting experiments obtained on [[Cdc2]] and B-myb promoters demonstrated E2F DNA binding site occupation during G0 and early G1, when E2F is in transcriptional repressive complexes with the pocket proteins.
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| pRb is one of the targets of the oncogenic [[human papilloma virus]] protein E7, and human [[adenovirus]] protein E1A. By binding to pRB, they stop the regulation of E2F transcription factors and drive the cell cycle to enable virus genome replication.
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| === Activators: E2F1, E2F2, E2F3a ===
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| Activators are maximally expressed late in G1 and can be found in association with E2F regulated promoters during the G1/S transition. The activation of E2F-3a genes follows upon the [[growth factor]] stimulation and the subsequent [[phosphorylation]] of the E2F inhibitor retinoblastoma protein, [[retinoblastoma protein|pRB]]. The [[phosphorylation]] of pRB is initiated by [[cyclin D]]/[[cdk4]], [[cdk6]] complex and continued by cyclin E/cdk2. Cyclin D/cdk4,6 itself is activated by the [[MAPK]] signaling pathway.
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| When bound to E2F-3a, pRb can directly repress E2F-3a target genes by recruiting chromatin remodeling complexes and histone modifying activities (e.g. histone deacetylase, [[HDAC]]) to the promoter.
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| === Inhibitors: E2F3b, E2F4, E2F5, E2F6, E2F7, E2F8 ===
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| * E2F3b, E2F4, E2F5 are expressed in quiescent cells and can be found associated with E2F-binding elements on E2F-target promoters during G0-phase. E2F-4 and 5 preferentially bind to p107/p130.
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| * E2F-6 acts as a transcriptional repressor, but through a distinct, pocket protein independent manner. E2F-6 mediates repression by direct binding to [[polycomb-group proteins]] or via the formation of a large multimeric complex containing Mga and Max proteins.
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| * E2F7 and E2F8 proteins can function as repressors independently of DP interaction. They are unique in having a duplicated conserved E2F-like DNA-binding domain and in lacking a DP1,2-dimerization domain. The exact mechanism of mediating repression is not yet understood.
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| ==Transcriptional targets==
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| * Cell cycle: CCNA1,2, CCND1,2, [[Cyclin-dependent kinase|CDK2]], MYB, E2F1,2,3, TFDP1, CDC25A
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| * Negative regulators: E2F7, [[Retinoblastoma protein|RB1]], TP107, TP21
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| * Checkpoints: [[TP53]], [[BRCA1]],2, BUB1
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| * Apoptosis: TP73, APAF1, [[Caspase|CASP3]],7,8, MAP3K5,14
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| * Nucleotide synthesis: [[thymidine kinase]] (tk), thymidylate synthase (ts), [[Dihydrofolate reductase|DHFR]]
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| * DNA repair: BARD1, RAD51, UNG1,2, FANCA, FANCC, FANCJ
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| * DNA replication: [[PCNA]], [[histone]] H2A, [[DNA polymerase|DNA pol]]<math>\alpha</math> and <math>\delta</math>, RPA1,2,3, CDC6, MCM2,3,4,5,6,7
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| <ref name="pmid15838516">{{cite journal | author = Cobrinik D | title = Pocket proteins and cell cycle control | journal = Oncogene | volume = 24 | issue = 17 | pages = 2796–809 | year = 2005 | pmid = 15838516 | doi = 10.1038/sj.onc.1208619 }}</ref>
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| <ref name="pmid15722552">{{cite journal | author = Maiti B, Li J, de Bruin A, Gordon F, Timmers C, Opavsky R, Patil K, Tuttle J, Cleghorn W, Leone G | title = Cloning and characterization of mouse E2F8, a novel mammalian E2F family member capable of blocking cellular proliferation | journal = J. Biol. Chem. | volume = 280 | issue = 18 | pages = 18211–20 | year = 2005 | pmid = 15722552 | doi = 10.1074/jbc.M501410200 }}</ref>
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| <ref name="pmid12004135">{{cite journal | author = Ogawa H, Ishiguro K, Gaubatz S, Livingston DM, Nakatani Y | title = A complex with chromatin modifiers that occupies E2F- and Myc-responsive genes in G0 cells | journal = Science | volume = 296 | issue = 5570 | pages = 1132–6 | year = 2002 | pmid = 12004135 | doi = 10.1126/science.1069861 }}</ref> | |
| <ref name="pmid8524257">{{cite journal | author = Tommasi S, Pfeifer GP | title = In vivo structure of the human cdc2 promoter: release of a p130-E2F-4 complex from sequences immediately upstream of the transcription initiation site coincides with induction of cdc2 expression | journal = Mol. Cell. Biol. | volume = 15 | issue = 12 | pages = 6901–13 | year = 1995 | pmid = 8524257 | doi = | issn = | url = http://mcb.asm.org/cgi/content/abstract/15/12/6901 | format = abstract | pmc = 230945 }}</ref>
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| <ref name="pmid8599118">{{cite journal | author = Zwicker J, Liu N, Engeland K, Lucibello FC, Müller R | title = Cell cycle regulation of E2F site occupation in vivo | journal = Science | volume = 271 | issue = 5255 | pages = 1595–7 | year = 1996 | pmid = 8599118 | doi = 10.1126/science.271.5255.1595 }}</ref>
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| <ref name="Tategu">{{cite journal | author = Tategu M, Arauchi T,Tanaka R,Nakagawa H, Yoshida K | title = Systems Biology-Based Identifi cation of Crosstalk between E2F Transcription Factors and the Fanconi Anemia Pathway | journal = Gene Regulation and Systems Biology | volume = 1 | issue = 1 | pages = 1–7 | year = 2007 | pmid = | doi = | issn = | url = http://la-press.com/article.php?article_id=219 }}</ref>
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| ==See also==
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| *[[Transcription factor DP]]
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| ==References==
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| {{Reflist|2}}
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| ==External links==
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| * {{MeshName|E2F+Transcription+Factors}}
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| * [http://www.sdbonline.org/fly/newgene/e2f.htm ''Drosophila'' ''E2F transcription factor'' - The Interactive Fly]
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| * [http://www.sdbonline.org/fly/newgene/e2fsnd-1.htm ''Drosophila'' ''E2F transcription factor 2'' - The Interactive Fly]
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| {{Transcription factors|g3}}
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| {{Cell cycle proteins}}
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| {{reflist}}
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| [[Category:Cell cycle]]
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| [[Category:Transcription factors]]
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New Condominium is an upcoming combined improvement located in Yishun Central, Northern Region of Singapore. This development is strategically situated next to Northpoint Buying Centre and reverse of Yishun Train Station. New Condominium is a ninety nine years leasehold mission that has a site area of roughly 442,397 sq. toes. Upon completion it's going to comprise of an estimated 890 residential items and 359,084 sq. ft of commercial space.
Evaluation now by visiting the brand new condominium pages on our site, each displaying comprehensive details and the newest info of each new launch. You can too contact us directly to receive fast & correct answers to all of your questions with top of the line service. The nearby private housing developments are mainly low-rise landed property giving extra privacy and exclusivity to the new development. The virtually unspoil environment is what differentiates this growth from the encompassing ones (VII) Park Connector With solely 118 beautiful units, Belgravia Villas at Ang Mo Kio is the most anticipated freehold cluster home launch in 2013! Commonwealth Towers Condo beside Queenstown MRT Station Compass Point (Approx 1.6KM) Colleges Nearby Riverbank Fernvale Apartment
With Singapore conserving its greenery and with the town sky view being the attraction to many, it is no wonder that increasingly condos are being developed on the island. Many future investors are putting more value on items with a view than these with out one. Thus, this can be one of the reasons too as to why your unit of alternative is either with a view or without. I'm not encouraging you to ‘leap' into a property buy, however to perform a little research and make a judgement name. The Crest Rental at Prince Charles Crest, Wing Tai upcomingcondo Launch now open for expression of curiosity. Calculation of using CPF funds for Property Less than 60 years however more than 30 years New Apartment in 2013 September New Condo 2013 August New Condo Waterfront @ Faber COULD
Fitness enthusiast and nature lovers will find the nearby Bishan Ang Mo Kio park, Macritchie reservoir, nature reserve, golf course, stadium, swimming advanced, sports corridor a plus plus point as a resident of Sky Vue rental. Famend instructional institution are also within close proximity of Sky Vue rental. There is a choice for everybody at Sky Vue apartment, with unit mixture of 1 bed room, 2 bed room, 2 bed room suite, 3 bedroom as well as penthouses. View Sky Vue Condo floor plan Sky Vue Condominium - Undertaking Description Bartley Ridge is a brand new rental situated within a singapore new launch; mouse click the next web site, residential enclave along Mount Vernon Street, with Bartley MRT station nearby. Learn More → The Sorrento is an Exciting New Freehold Condominium providing the Ultimate Luxurious dwelling within the West. Read Extra →
Now that you have all these to consider, it's a good suggestion to search for for real estate brokers that may aid you in making the right action of investing on the proper property once you are ready. A dependable agent will just be sure you have the proper funds for a new rental launch investing. With out figuring out the precise quantity of how a lot you're keen to spend, you can be quick in the long run since it's a must to guantee that the budget also covers the upkeep bills. These expenses will steadily enhance yr by year and if you are investing without a monetary plan, the dream of getting your individual non-public residential unit will never be a reality.
Ocean Membership Resorts in Turks & Caicos is offering as much as 25 % low cost on rooms this Cyber Monday. Book online and use promo code "CYBER" to receive 20 % off all room categories and receive a $200 lodge credit score for 5 or extra night time stays for travel between January three and February 7, 2014. Or get 25 percent off juniors, one, two and three bedrooms and receive a $200 lodge credit for 5 or more night stays for travel between May 1 and December 18, 2014. Can't be combined with any further low cost, including EBB. The Cyber Monday sale is 24 hours solely.
This high-rise luxurious condominium can also be a really brief walk from Queenstown MRT station, which gives handy travel to all parts of Singapore on the MRT strains island huge. Even throughout the property itself, daily needs are nicely taken care of, including for recreation and leisure. I still bear in mind the detrimental voices saying property prices will drop when I first began out in actual property in 2010. Trying on the chart now, I'm sure your reply can be – ‘Yes, I'd probably buy in 2006 or 2010.' Now the correct time to purchase a New Launch Condo? 28RC Suites is a Freehold Blended Growth situated at 28 Race Course Lane in prime district 8 of Singapore. Located within walking distance to Farrer Read Extra Continuereading "Trilive at Kovan Preview Launch Soon"
Vero Seaside Resort & Spa and Kimpton's Surfcomber in South Seashore and Miami are offering two deals. The first is 15 p.c off the perfect obtainable price while you stay for 2 nights. The second deal is 20 p.c off one of the best out there charge if you keep for 3 nights. Company reserving at Surfcomber will receive a free appetizer at the Social Membership while visitors reserving on the Vero receive a free appetizer on the Cobalt. This off is obtainable for travel by means of Christmas 2013. To make reservations at Surfcomber, call 800-994-62013 or visit the lodge's website For reservations at Vero Beach, name 1-866-602-8376 or go to the resort's website Ensure that to use the code CYBER for each deals.