AC T02905
AS T00802.
XX
ID T02905
XX
DT 17.01.2000 (created); sur.
DT 01.10.2012 (updated); mkl.
CO Copyright (C), QIAGEN.
XX
FA LEF-1-isoform1
XX
SY hLEF-1; human LEF-1; Lymphocyte enhancer binding factor 1; lymphoid enhancer binding factor 1; lymphoid enhancing factor 1; TCF-1alpha; TCF1-alpha; transcription factor 1-alpha.
XX
OS human, Homo sapiens
OC eukaryota; animalia; metazoa; chordata; vertebrata; tetrapoda; mammalia; eutheria; primates
XX
GE G013559 LEF1; HGNC: Lef1.
XX
CL C0015; HMG; 4.1.3.0.4.1.
XX
SZ 399 AA; 44.2 kDa (cDNA) (calc.), 55 kDa (SDS)
XX
SQ MPQLSGGGGGGGGDPELCATDEMIPFKDEGDPQKEKIFAEISHPEEEGDLADIKSSLVNE
SQ SEIIPASNGHEVARQAQTSQEPYHDKAREHPDDGKHPDGGLYNKGPSYSSYSGYIMMPNM
SQ NNDPYMSNGSLSPPIPRTSNKVPVVQPSHAVHPLTPLITYSDEHFSPGSHPSHIPSDVNS
SQ KQGMSRHPPAPEIPTFYPLSPGGVGQITPPLGWQGQPVYPITGGFRQPYPSSLSVDTSMS
SQ RFSHHMIPGPPGPHTTGIPHPAIVTPQVKQEHPHTDSDLMHVKPQHEQRKEQEPKRPHIK
SQ KPLNAFMLYMKEMRANVVAECTLKESAAINQILGRRWHALSREEQAKYYELARKERQLHM
SQ QLYPGWSARDNYGKKKKRKREKLQESASGTGPRMTAAYI
XX
SC from ref. [1] and ref. [20]; AA 389-399 are dedicated as LEF-1N tail ref. [20]
XX
FT 1 56 
beta-catenin interacting domain [17].
FT 1 60 
beta-catenin interacting domain [20].
FT 1 71 
encoded by exon 1 [20].
FT 72 93 
encoded by exon 2 [20].
FT 80 135 
trans-activation domain A [4].
FT 94 133 
encoded by exon 3 [20].
FT 134 182 
encoded by exon 4 [20].
FT 174 256 
trans-activation domain B [4].
FT 183 213 
encoded by exon 5 [20].
FT 214 241 
encoded by exon 6 [20].
FT 242 281 encoded by exon 7 [20].
FT 244 286 proline and histidine rich region (17/43) [1].
FT 282 336 encoded by exon 8 [20].
FT 295 362 HMG domain [1].
FT 297 364 HMG domain [20].
FT 298 368 SM00398; hmgende2.
FT 299 367 PF00505; HMG (high mobility group) box.
FT 299 367 PS50118; HMG_BOX_2.
FT 337 372 encoded by exon 9 [20].
FT 372 383 NLS (nuclear localisation signal) [20].
FT 372 399 encoded by exon 10 [20].
FT 374 382 B box (essential for nuclear transposition) [13].
FT 389 399 LEF-1N tail [20].
XX
SF the LEF-1-isoform1 gene (52 kb) is located on chromosome 4, exon structure: 1,2,3, 3a, 3b, 4,5,6,7,8,9,10,11,12 [20];
SF sequence-specific DNA-binding is mediated by the disordered N-terminal part of the L-shaped HMG domain and by its third alpha-helix [5];
SF binds to pyrimidine-rich elements 5�-YCTTTG-3� [1];
SF no appreciable T cell-specific enhancer activity in the absence of the flanking CRE and TCF-2alpha/ets-binding sites --> direct interaction with CREB and TCF-2alpha/ets proteins? [2];
SF hLEF-1-isoform1 binds DNA as a monomer but cannot function on its own to enhance transcription [4];
SF formerly TCF-1alpha;
SF a shorter cDNA clone reveals a protein which lacks AA 214-241 [1];
SF gene located on chromosome 4 [3];
SF for in vitro binding to the wild-type hLEF site in the TCRalpha enhancer a truncated protein bearing AA 297-377 is sufficient [4];
SF alanine substitution mutagenesis and EMSA shows that AA 25-27 and 32-34 are not necessary for beta-catenin binding [18];
SF the transactivating domain normally provided by beta-catenin can be replaced by other transactivating domains [19];
XX
CP T-cells; thymus.
XX
FF contains a potent transcriptional activation domain which mediates context-specific activation of the TCFalpha enhancer [4];
FF can form a complex with beta-catenin (in the nucleus) and thus activates gene transcription;
FF member of the Wnt-/ Wingless-signal transduction cascade;
FF uncontrolled activation of gene transcription by the beta-catenin/ LEF-1-isoform1 complex may contribute to tumor progression;
FF c-myc and cyclin D1 contain LEF-1-isoform1 binding sequences in promoter region [8];
FF upon Wnt-1 signaling combined with beta-catenin binding the transcriptional activity of LEF-1-isoform1 rises;
FF LEF-1-isoform1 can activate transcription thus from a synthetic enhancer containing multimerized binding sites in contrast to the activation of the TCFalpha enhancer where LEF-1-isoform1 can only activate transcription upon a specific context of transcription factors;
FF in the TCFalpha enhancer LEF-1-isoform1 collaborates with AML1-, Ets-1 and CREB;
FF the activation potential in this context is further dependent on ALY which associates with the context dependent activation domains of LEF-1-isoform1 and AML-1;
FF taken together LEF-1-isoform1 can exert two different roles: in association with beta-Catenin it can mediate transcriptional activation in a context-independent manner, whereas it regulates - together with ALY - transcription in a context specific way [18];
FF the ability of LEF-1-isoform1 to induce oncogenic transformation was shown by generating covalent linked LEF-1-isoform1 and beta-catenin (or other transactivating domains) [19];
FF beta-catenin stabilizing mutations result in LEF-1-isoform1 transactivation leading to development of human tumours of hair matrix differentiation [15];
XX
IN T02872 beta-catenin; human, Homo sapiens.
IN T02984 beta-catenin; mouse, Mus musculus.
IN T05686 Grg4; mouse, Mus musculus.
IN T04096 Smad3-isoform1; human, Homo sapiens.
XX
MX M00978 V$LEF1TCF1_Q4.
MX M00805 V$LEF1_Q2.
MX M01022 V$LEF1_Q2_01.
MX M07046 V$LEF1_Q3.
MX M07605 V$LEF1_Q4.
MX M02019 V$LEF1_Q5.
MX M03794 V$LEF1_Q5_01.
MX M08902 V$TCF7RELATED_Q4.
XX
BS R08638.
BS R04278.
BS R08588.
BS R08576.
BS R15488.
BS R28283.
BS R15455.
BS R15489.
BS R15490.
BS R08631.
BS R14795.
BS R14796.
BS R14797.
BS R15773.
BS R03470.
BS R18127.
BS R18128.
BS R18130.
BS R02248.
BS R08604.
BS R08818.
BS R08819.
BS R08649.
BS R08633.
BS R08634.
BS R08589.
BS R08591.
BS R08820.
BS R08821.
XX
DR TRANSPATH: MO000018860.
DR TRANSCOMPEL: C00194.
DR TRANSCOMPEL: C00268.
DR TRANSCOMPEL: C00269.
DR EMBL: AF203908; AF203908.
DR UniProtKB: Q9UJU2-1; LEF1_HUMAN.
XX
RN [1]; RE0000694.
RX PUBMED: 2010090.
RA Waterman M. L., Fischer W. H., Jones K. A.
RT A thymus-specific member of the HMG protein family regulates the human T-cell receptor Calpha enhancer
RL Genes Dev. 5:656-669 (1991).
RN [2]; RE0001944.
RX PUBMED: 2083253.
RA Waterman M. L., Jones K.
RT Purification of TCF-1alpha, a T-cell-specific transcription factor that activates the T-cell receptor Calpha gene enhancer in a context-dependent manner
RL New Biol. 2:621-636 (1990).
RN [3]; RE0004363.
RX PUBMED: 1752444.
RA Giese K., Amsterdam A., Grosschedl R.
RT DNA-binding properties of the HMG domain of the lymphoid-specific transcriptional regulator LEF-1
RL Genes Dev. 5:2567-2578 (1991).
RN [4]; RE0004365.
RX PUBMED: 8253387.
RA Carlsson P., Waterman M. L., Jones K. A.
RT The hLEF/TCF-1alpha HMG protein contains a context-dependent transcriptional activation domain that induces the TCRalpha enhancer in T cells
RL Genes Dev. 7:2418-2430 (1993).
RN [5]; RE0004366.
RX PUBMED: 7988561.
RA Read C. M., Cary P. D., Preston N. S., Lnenicek-Allen M., Crane-Robinson C.
RT The DNA sequence specificity of HMG boxes lies in the minor wing of the structure
RL EMBO J. 13:5639-5646 (1994).
RN [6]; RE0006108.
RX PUBMED: 8757136.
RA Behrens J., von Kries J. P., Kuehl M., Bruhn L., Wedlich D., Grosschedl R., Birchmeier W.
RT Functional interaction of beta-catenin with the transcription factor LEF -1
RL Nature 382:638-642 (1996).
RN [7]; RE0011357.
RX PUBMED: 7657162.
RA Sheridan P. L., Sheline C. T., Cannon K., Voz M. L., Pazin M. J., Kadonaga J. T., Jones K. A.
RT Activation of the HIV-1 enhancer by the LEF-1 HMG protein on nucleosome-assembled DNA in vitro
RL Genes Dev. 9:2090-2104 (1995).
RN [8]; RE0014041.
RX PUBMED: 10318916.
RA Shtutman M., Zhurinsky J., Simcha I., Albanese C., D'Amico M., Pestell R., Ben-Ze'ev A.
RT The cyclin D1 gene is a target of the beta-catenin/ Lef-1 pathway
RL Proc. Natl. Acad. Sci. USA 96:5522-5527 (1999).
RN [9]; RE0014048.
RX PUBMED: 9371763.
RA Giese K., Pagel J., Grosschedl R.
RT Functional analysis of DNA bending and unwinding by the high mobility group domain of LEF-1
RL Proc. Natl. Acad. Sci. USA 94:12845-12850 (1997).
RN [10]; RE0014049.
RX PUBMED: 9016677.
RA Haynes T. L., Thomas M. B., Dusing M. R., Valerius M. T., Potter S. S., Wiginton D. A.
RT An enhancer LEF-1/TCF-1 site is essential for insertin site-independent transgene expression in thymus
RL Nucleic Acids Res. 24:5034-5044 (1996).
RN [11]; RE0014050.
RX PUBMED: 9308964.
RA Brannon M., Gomperts M., Sumoy L., Moon R. T., Kimelman D.
RT A beta-catenin/XTcf-3 complex binds to the siamois promoter to regulate dorsal axis specification in Xenopus
RL Genes Dev. 11:2359-2370 (1997).
RN [12]; RE0014053.
RX PUBMED: 10495268.
RA McGrew L. L., Takemaru K.-I., Bates R., Moon R. T.
RT Direct regulation of the Xenopus engrailed-2 promoter by the Wnt signaling pathway, and a molecular screen for Wnt-responsive genes, confirm a role for Wnt signaling during neural patterning in Xenopus
RL Mech. Dev. 87:21-32 (1999).
RN [13]; RE0014054.
RX PUBMED: 8631802.
RA Prieve M. G., Guttridge K. L., Munguia J. E., Waterman M. L.
RT The nuclear localization signal of lymphoid enhancer factor-1 is recognized by two differentially expressed Srp1-nuclear localization sequence receptor proteins
RL J. Biol. Chem. 271:7654-7658 (1996).
RN [14]; RE0014090.
RX PUBMED: 9441678.
RA McKendry R., Hsu S.-C., Harland R. M., Grosschedl R.
RT LEF-1/TCF proteins mediate Wnt-inducible transcription from Xenopus nodal-related 3 promoter
RL Dev. Biol. 192:420-431 (1997).
RN [15]; RE0014096.
RX PUBMED: 10192393.
RA Chan E. F., Gat U., McNiff J. M., Fuchs E.
RT A common human skin tumour is caused by activating mutations in beta-catenin
RL Nat. Genet. 21:410-413 (1999).
RN [16]; RE0014099.
RX PUBMED: 10409747.
RA Gradl D., Kuhl M., Wedlich D.
RT The Wnt/Wg signal transducer beta-catenin controls fibronectin expression
RL Mol. Cell. Biol. 19:5576-5587 (1999).
RN [17]; RE0014185.
RX PUBMED: 8892228.
RA Huber O., Korn R., McLaughlin J., Ohsugi M., Herrmann B. G., Kemler R.
RT Nuclear localization of beta-catenin by interaction with transcription factor LEF-1
RL Mech. Dev. 59:3-10 (1996).
RN [18]; RE0014336.
RX PUBMED: 9671490.
RA Hsu S.-C., Galceran J., Grosschedl R.
RT Modulation of transcriptional regulation by LEF-1 in response to Wnt-1 signaling and association with beta-catenin
RL Mol. Cell. Biol. 18:4807-4818 (1998).
RN [19]; RE0014351.
RX PUBMED: 9874785.
RA Aoki M., Hecht A., Kruse U., Kemler R., Vogt P. K.
RT Nuclear endpoint of Wnt signaling: neoplastic transformation induced by transactivating lymphoid-enhancing factor 1
RL Proc. Natl. Acad. Sci. USA 96:139-144 (1999).
RN [20]; RE0014765.
RX PUBMED: 10756202.
RA Hovanes K., Li T. W. H., Waterman M. L.
RT The human LEF-1 gene contains a promoter preferentially active in lymphocytes and encodes multiple isoforms derived from alternative splicing
RL Nucleic Acids Res. 28:1994-2003 (2000).
XX
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