basic helix loop helix leucine zipper transcription factors


Summary: A family of transcription factors that contain regions rich in basic residues, LEUCINE ZIPPER domains, and HELIX-LOOP-HELIX MOTIFS.

Top Publications

  1. de Pontual L, Mathieu Y, Golzio C, Rio M, Malan V, Boddaert N, et al. Mutational, functional, and expression studies of the TCF4 gene in Pitt-Hopkins syndrome. Hum Mutat. 2009;30:669-76 pubmed publisher
    ..In summary, we further delineate an underdiagnosed mental retardation syndrome, highlighting TCF4 function during development and facilitating diagnosis within the first year of life. ..
  2. Yu F, Goh S, Dai R, Luo Y. Adenosine-containing molecules amplify glucose signaling and enhance txnip expression. Mol Endocrinol. 2009;23:932-42 pubmed publisher
    ..The regulatory role of these molecules may be exerted via amplifying glucose signaling. Hence, this revelation may pave the way for interventions aimed toward metabolic disorders resulting from abnormal glucose homeostasis. ..
  3. Singh S, Gramolini A. Characterization of sequences in human TWIST required for nuclear localization. BMC Cell Biol. 2009;10:47 pubmed publisher
    ..Our study demonstrates the presence of two putative NLS motifs in H-TWIST and suggests that these NLS sequences are functional. Furthermore, we identified and confirmed the interaction of TWIST with a novel protein candidate TCF-4. ..
  4. Hsiao S, Huang K, Chang H, Chen S. P/CAF rescues the Bhlhe40-mediated repression of MyoD transactivation. Biochem J. 2009;422:343-52 pubmed publisher
    ..Bhlhe40 interacted with P/CAF and this interaction disrupted the interaction between P/CAF and MyoD. These results suggest that Bhlhe40 functions as a repressor of MyoD by binding to adjacent E-boxes and sequestering P/CAF from MyoD. ..
  5. Argani P, Hicks J, De Marzo A, Albadine R, Illei P, Ladanyi M, et al. Xp11 translocation renal cell carcinoma (RCC): extended immunohistochemical profile emphasizing novel RCC markers. Am J Surg Pathol. 2010;34:1295-303 pubmed publisher
    ..Elevated expression of phosphorylated S6 in Xp11 translocation RCC suggests the mTOR pathway as an attractive potential therapeutic target for these neoplasms...
  6. Armah H, Parwani A. Xp11.2 translocation renal cell carcinoma. Arch Pathol Lab Med. 2010;134:124-9 pubmed publisher
    ..2 translocation RCC with respect to age, clinical behavior, and molecular abnormalities. ..
  7. Kato Z, Morimoto W, Kimura T, Matsushima A, Kondo N. Interstitial deletion of 18q: comparative genomic hybridization array analysis of 46, XX,del(18)(q21.2.q21.33). Birth Defects Res A Clin Mol Teratol. 2010;88:132-5 pubmed publisher
    ..Interstitial deletion of chromosome 18q is rare, making it difficult to assign phenotypes to particular cytogenetic deletions...
  8. Mahmoudi T, Li V, Ng S, Taouatas N, Vries R, Mohammed S, et al. The kinase TNIK is an essential activator of Wnt target genes. EMBO J. 2009;28:3329-40 pubmed publisher
    ..This kinase may present an attractive candidate for drug targeting in colorectal cancer. ..
  9. Zhang H, Zhang H, Zhang Y, Ng S, Ren F, Wang Y, et al. Dishevelled-DEP domain interacting protein (DDIP) inhibits Wnt signaling by promoting TCF4 degradation and disrupting the TCF4/beta-catenin complex. Cell Signal. 2010;22:1753-60 pubmed publisher
    ..Our results indicate that DDIP is a negative regulator of the canonical Wnt signaling. ..

More Information


  1. Huang C, Cheng J, Kitajima K, Nakano T, Yeh C, Chong K, et al. Disabled-2 is required for mesoderm differentiation of murine embryonic stem cells. J Cell Physiol. 2010;225:92-105 pubmed publisher
    ..This study thereby defines a role of DAB2 in fate determination of ESCs and suggests the presence of a DAB2-associated regulatory circuit in the control of mesoderm differentiation. ..
  2. Svec J, Ergang P, Mandys V, Kment M, Pacha J. Expression profiles of proliferative and antiapoptotic genes in sporadic and colitis-related mouse colon cancer models. Int J Exp Pathol. 2010;91:44-53 pubmed publisher
  3. Liu X, Luo M, Xie W, Wells J, Goodheart M, Engelhardt J. Sox17 modulates Wnt3A/beta-catenin-mediated transcriptional activation of the Lef-1 promoter. Am J Physiol Lung Cell Mol Physiol. 2010;299:L694-710 pubmed publisher
  4. Fre S, Pallavi S, Huyghe M, Lae M, Janssen K, Robine S, et al. Notch and Wnt signals cooperatively control cell proliferation and tumorigenesis in the intestine. Proc Natl Acad Sci U S A. 2009;106:6309-14 pubmed publisher
    ..Importantly, our experimental evidence raises the possibility that Notch activation might be an essential initial event triggering colorectal cancer...
  5. McDuff F, Naud J, Montagne M, Sauvé S, Lavigne P. The Max homodimeric b-HLH-LZ significantly interferes with the specific heterodimerization between the c-Myc and Max b-HLH-LZ in absence of DNA: a quantitative analysis. J Mol Recognit. 2009;22:261-9 pubmed publisher
    ..From a systems biology perspective, our routines may be of general interest as they offer the opportunity to treat many competing equilibriums in order to predict the probability of existence of protein complexes. ..
  6. Gulacsi A, Anderson S. Beta-catenin-mediated Wnt signaling regulates neurogenesis in the ventral telencephalon. Nat Neurosci. 2008;11:1383-91 pubmed publisher
  7. Taddeucci G, Bonuccelli A, Mantellassi I, Orsini A, Tarantino E. Pitt-Hopkins syndrome: report of a case with a TCF4 gene mutation. Ital J Pediatr. 2010;36:12 pubmed publisher
    ..We will discuss the clinical and genetic diagnosis of a child with severe psychomotor delay, who at 3 years of age presented with paroxysms of hyperpnea-apnea and seizures unrelated to breathing anomalies...
  8. Been L, Nath S, Ralhan S, Wander G, Mehra N, Singh J, et al. Replication of association between a common variant near melanocortin-4 receptor gene and obesity-related traits in Asian Sikhs. Obesity (Silver Spring). 2010;18:425-9 pubmed publisher
    ..These observations demonstrate that the genetic variation in MC4R locus can have a moderate contribution in the regional fat deposition and development of central obesity in Asian Indians. ..
  9. Pan L, Chen Y, Huang H, Zhang L, Liu R, Li X, et al. G771C Polymorphism in the MLXIPL Gene Is Associated with a Risk of Coronary Artery Disease in the Chinese: A Case-Control Study. Cardiology. 2009;114:174-8 pubmed publisher
    ..28, 95% CI 1.061-1.542; p < 0.05). The gene sequence variation in the MLXIPL gene may serve as a novel genetic marker for the risk of significant CAD. ..
  10. Park C, Choi S, Kang S, Kang J, Ahn B, Kim H, et al. Nonstructural 5A protein activates beta-catenin signaling cascades: implication of hepatitis C virus-induced liver pathogenesis. J Hepatol. 2009;51:853-64 pubmed publisher
    ..This modulation is accomplished by the protein interplay between viral and cellular signaling transducer. These data suggest that NS5A protein may directly be involved in Wnt/beta-catenin-mediated liver pathogenesis. ..
  11. Koslowski M, Beisner J, Stange E, Wehkamp J. Innate antimicrobial host defense in small intestinal Crohn's disease. Int J Med Microbiol. 2010;300:34-40 pubmed publisher
    ..Thus, Paneth cells seem to be key player emphazising a paramount importance of antimicrobial host defense in small intestinal CD pathogenesis. ..
  12. Lee T, Jorgensen P, Bognar A, Peyraud C, Thomas D, Tyers M. Dissection of combinatorial control by the Met4 transcriptional complex. Mol Biol Cell. 2010;21:456-69 pubmed publisher
    ..Taken together, Met4 cofactors use a variety of mechanisms to allow differential transcription of target genes in response to various cues. ..
  13. Gallant P, Steiger D. Myc's secret life without Max. Cell Cycle. 2009;8:3848-53 pubmed
    ..The discovery of these Max-independent functions changes our understanding of basic Myc biology and it may affect pharmaceutical approaches to inhibiting Myc activity. ..
  14. Kim M, Go Y, Lee S, Kim Y, Shin J, Min M, et al. Seed-expressed casein kinase I acts as a positive regulator of the SeFAD2 promoter via phosphorylation of the SebHLH transcription factor. Plant Mol Biol. 2010;73:425-37 pubmed publisher
    ..This co-expression revealed that SeCKI enhanced the SebHLH-mediated transactivation of the SeFAD2 gene promoter via phosphorylation of the SebHLH transcription factor...
  15. Nath N, Vassell R, Chattopadhyay M, Kogan M, Kashfi K. Nitro-aspirin inhibits MCF-7 breast cancer cell growth: effects on COX-2 expression and Wnt/beta-catenin/TCF-4 signaling. Biochem Pharmacol. 2009;78:1298-304 pubmed publisher
    ..p-NO-ASA blocked the cell cycle transition at S to G2/M phase. These studies suggest a targeted chemopreventive/chemotherapeutic potential for NO-ASA against breast cancer. ..
  16. Zhong M, De Angelo P, Osborne L, Keane Tarchichi M, Goldfischer M, Edelmann L, et al. Dual-color, break-apart FISH assay on paraffin-embedded tissues as an adjunct to diagnosis of Xp11 translocation renal cell carcinoma and alveolar soft part sarcoma. Am J Surg Pathol. 2010;34:757-66 pubmed publisher
    ..This break-apart FISH assay is a relatively quick procedure for detecting Xp11.2 RCC and ASPS translocations and can be applied to archival paraffin-embedded tissue. ..
  17. Wu K, Cappel D, Martinez M, STAFFORD J. Impaired-inactivation of FoxO1 contributes to glucose-mediated increases in serum very low-density lipoprotein. Endocrinology. 2010;151:3566-76 pubmed publisher
    ..These data suggest that glucose more potently promotes increased serum VLDL when insulin action is impaired, with either low insulin levels or disrupted downstream signaling to the transcription factor FoxO1. ..
  18. Kavak E, Najafov A, Ozturk N, Seker T, Cavusoglu K, Aslan T, et al. Analysis of the Wnt/B-catenin/TCF4 pathway using SAGE, genome-wide microarray and promoter analysis: Identification of BRI3 and HSF2 as novel targets. Cell Signal. 2010;22:1523-35 pubmed publisher
    ..BRI3 and HSF2 were identified as novel targets of Wnt/beta-catenin signaling after combined analysis and confirming experiments including qRT-PCR, ChIP, luciferase assay and lithium treatment. ..
  19. Medendorp K, van Groningen J, Vreede L, Hetterschijt L, Brugmans L, van den Hurk W, et al. The renal cell carcinoma-associated oncogenic fusion protein PRCCTFE3 provokes p21 WAF1/CIP1-mediated cell cycle delay. Exp Cell Res. 2009;315:2399-409 pubmed publisher
  20. Domenzain Reyna C, Hernandez D, Miquel Serra L, Docampo M, Badenas C, Fabra A, et al. Structure and regulation of the versican promoter: the versican promoter is regulated by AP-1 and TCF transcription factors in invasive human melanoma cells. J Biol Chem. 2009;284:12306-17 pubmed publisher
    ..These results showing that AP-1 and TCF-4 binding sites are the main regulatory regions directing versican production provide new insights into versican promoter regulation during melanoma progression. ..
  21. Schwarz T, Murphy S, Sohn C, Mansky K. C-TAK1 interacts with microphthalmia-associated transcription factor, Mitf, but not the related family member Tfe3. Biochem Biophys Res Commun. 2010;394:890-5 pubmed publisher
  22. Jiang Z, Belforte J, Lu Y, Yabe Y, Pickel J, Smith C, et al. eIF2alpha Phosphorylation-dependent translation in CA1 pyramidal cells impairs hippocampal memory consolidation without affecting general translation. J Neurosci. 2010;30:2582-94 pubmed publisher
    ..The present study sheds light on the critical importance of gene-specific translations for hippocampal memory consolidation. ..
  23. Argani P, Aulmann S, Illei P, Netto G, Ro J, Cho H, et al. A distinctive subset of PEComas harbors TFE3 gene fusions. Am J Surg Pathol. 2010;34:1395-406 pubmed publisher
    ..Despite significant morphologic and immunohistochemical overlap with other PEComas, PEComas harboring TFE3 gene fusions may represent a distinctive entity. ..
  24. Kang D, Lee S, Yoon J, Park W, Choi K, Min D. Phospholipase D1 drives a positive feedback loop to reinforce the Wnt/beta-catenin/TCF signaling axis. Cancer Res. 2010;70:4233-42 pubmed publisher
  25. Wright J, Brown S, Cole M. Upregulation of c-MYC in cis through a large chromatin loop linked to a cancer risk-associated single-nucleotide polymorphism in colorectal cancer cells. Mol Cell Biol. 2010;30:1411-20 pubmed publisher
    ..The findings of these studies support a mechanism for intergenic SNPs that can promote cancer through the regulation of distal genes by utilizing preexisting large chromatin loops. ..
  26. Verzi M, Hatzis P, Sulahian R, Philips J, Schuijers J, Shin H, et al. TCF4 and CDX2, major transcription factors for intestinal function, converge on the same cis-regulatory regions. Proc Natl Acad Sci U S A. 2010;107:15157-62 pubmed publisher
    ..Co-occupancy of regulatory regions by signal-effector and tissue-restricted transcription factors may represent a general mechanism for ubiquitous signaling pathways to achieve tissue-specific outcomes...
  27. Perminow G, Beisner J, Koslowski M, Lyckander L, Stange E, Vatn M, et al. Defective paneth cell-mediated host defense in pediatric ileal Crohn's disease. Am J Gastroenterol. 2010;105:452-9 pubmed publisher
    ..The aim of this study was to evaluate human alpha-defensin-5 (HD-5) and TCF-4 in an independent cohort of pediatric CD patients...
  28. Koie T, Yoneyama T, Hashimoto Y, Kamimura N, Kusumi T, Kijima H, et al. An aggressive course of Xp11 translocation renal cell carcinoma in a 28-year-old man. Int J Urol. 2009;16:333-5 pubmed publisher
    ..The utility of immunohistochemistry using antibodies against TFE3 in RCC occurring in young adults may be necessary for accurate diagnosis. ..
  29. Chini A, Fonseca S, Chico J, Fernández Calvo P, Solano R. The ZIM domain mediates homo- and heteromeric interactions between Arabidopsis JAZ proteins. Plant J. 2009;59:77-87 pubmed publisher
    ..Finally, we show that interaction with MYC2 is a common feature of the JAZ family, as most JAZ proteins can bind MYC2 in pull-down and yeast two-hybrid assays. ..
  30. Gallant P. Drosophila Myc. Adv Cancer Res. 2009;103:111-44 pubmed publisher
    ..This review summarizes what the last decade has taught us about Myc biology in the fruit fly. ..
  31. Li Y, Liu Z, Zhang K, Chen X, Kong Q, Wu M, et al. Methylation-associated silencing of S100A4 expression in human epidermal cancers. Exp Dermatol. 2009;18:842-8 pubmed publisher
    ..Wnt activation and E-cadherin reduction and S100A4 down-regulation are paralleled molecular events in skin tumors, which may serve as the biomarkers for predicting epidermal cancer risk. ..
  32. Rena V, Angeletti S, Panzetta Dutari G, Genti Raimondi S. Activation of beta-catenin signalling increases StarD7 gene expression in JEG-3 cells. Placenta. 2009;30:876-83 pubmed publisher
    ..Collectively, these studies show that beta-catenin and TCF4 activate the human StarD7 gene interacting with its promoter region through Wnt/beta-catenin signalling. ..
  33. Martignoni G, Pea M, Gobbo S, Brunelli M, Bonetti F, Segala D, et al. Cathepsin-K immunoreactivity distinguishes MiTF/TFE family renal translocation carcinomas from other renal carcinomas. Mod Pathol. 2009;22:1016-22 pubmed publisher
    ..3) These results further support the concept that the overexpression of TFE3 or TFEB in these neoplasms activates the expression of genes normally regulated by microphthalmia transcription factor in other cell types. ..
  34. Wei W, Chua M, Grepper S, So S. Small molecule antagonists of Tcf4/beta-catenin complex inhibit the growth of HCC cells in vitro and in vivo. Int J Cancer. 2010;126:2426-36 pubmed publisher
    ..Our results suggest that these 3 antagonists of the Tcf4/beta-catenin complex are potential chemotherapeutic agents which may offer a pathway specific option for the clinical management of HCC. ..
  35. Kuroda N, Tamura M, Tanaka Y, Hes O, Michal M, Inoue K, et al. Adult-onset renal cell carcinoma associated with Xp11.2 translocations/TFE3 gene fusion with smooth muscle stroma and abnormal vessels. Pathol Int. 2009;59:486-91 pubmed publisher
    ..G-band karyotype was unsuccessful. Pathologists should pay attention to the afore-described unusual stromal reaction of adult-onset RCC associated with Xp11.2 translocations/TFE3 gene fusions. ..
  36. Pannequin J, Bonnans C, Delaunay N, Ryan J, Bourgaux J, Joubert D, et al. The wnt target jagged-1 mediates the activation of notch signaling by progastrin in human colorectal cancer cells. Cancer Res. 2009;69:6065-73 pubmed publisher
    ..These results suggest that progastrin could be instrumental in maintaining the concomitant activation of Wnt and Notch pathways in CRC cells, further highlighting the interest of progastrin targeting for the clinical management of CRC. ..
  37. Wang L, Li H, Zhang Y, Santella R, Weinstein I. HINT1 inhibits beta-catenin/TCF4, USF2 and NFkappaB activity in human hepatoma cells. Int J Cancer. 2009;124:1526-34 pubmed publisher
  38. Vendrell V, Summerhurst K, Sharpe J, Davidson D, Murphy P. Gene expression analysis of canonical Wnt pathway transcriptional regulators during early morphogenesis of the facial region in the mouse embryo. Gene Expr Patterns. 2009;9:296-305 pubmed publisher
  39. Sengupta P, Bouchie M, Kukuruzinska M. N-glycosylation gene DPAGT1 is a target of the Wnt/beta-catenin signaling pathway. J Biol Chem. 2010;285:31164-73 pubmed publisher
    ..Moreover, they suggest the existence of another regulatory mechanism involving the interaction of Tcf with ?-catenin at the DPAGT1 promoter...
  40. Xu J, Chen G, De Jong A, Shahravan S, Shin J. Max-E47, a designed minimalist protein that targets the E-box DNA site in vivo and in vitro. J Am Chem Soc. 2009;131:7839-48 pubmed publisher
  41. Huang Y, Shih H. Daxx positively modulates beta-catenin/TCF4-mediated transcriptional potential. Biochem Biophys Res Commun. 2009;386:762-8 pubmed publisher
    ..Together, our results suggest that Daxx functions as a positive coregulator in modulating the beta-catenin/TCF4-dependent transcriptional potential via TCF4 interaction. ..
  42. Zhang Z, Sun H, Dai H, Walsh R, Imakura M, Schelter J, et al. MicroRNA miR-210 modulates cellular response to hypoxia through the MYC antagonist MNT. Cell Cycle. 2009;8:2756-68 pubmed
    ..Thus, miR-210 influences the hypoxia response in tumor cells through targeting a key transcriptional repressor of the MYC-MAX network. ..
  43. Iizuka K, Takeda J, Horikawa Y. Glucose induces FGF21 mRNA expression through ChREBP activation in rat hepatocytes. FEBS Lett. 2009;583:2882-6 pubmed publisher
    ..Furthermore, deletion studies of mouse FGF21 gene promoter (-2000 to +65 bp) revealed a glucose responsive region between -74 and -52 bp. These findings suggest that FGF21 expression is regulated by ChREBP. ..
  44. Malouf G, Camparo P, Oudard S, Schleiermacher G, Theodore C, Rustine A, et al. Targeted agents in metastatic Xp11 translocation/TFE3 gene fusion renal cell carcinoma (RCC): a report from the Juvenile RCC Network. Ann Oncol. 2010;21:1834-8 pubmed publisher
    ..Median OS was 27 months with a 19 months median follow-up. In Xp11 translocation RCC, targeted therapy achieved objective responses and prolonged PFS similar to those reported for clear-cell RCC. ..
  45. Sun J, Wang D, Jin T. Insulin alters the expression of components of the Wnt signaling pathway including TCF-4 in the intestinal cells. Biochim Biophys Acta. 2010;1800:344-51 pubmed publisher
  46. Dehnhardt C, Venkatesan A, Chen Z, Ayral Kaloustian S, Dos Santos O, Delos Santos E, et al. Design and synthesis of novel diaminoquinazolines with in vivo efficacy for beta-catenin/T-cell transcriptional factor 4 pathway inhibition. J Med Chem. 2010;53:897-910 pubmed publisher
    ..Subsequently, 9 was tested for efficacy in a beta-catenin/RKE-mouse xenograft, where it led to more then 50% decrease in tumor volume. ..
  47. Navarro D, Agra N, Pestaña A, Alonso J, González Sancho J. The EWS/FLI1 oncogenic protein inhibits expression of the Wnt inhibitor DICKKOPF-1 gene and antagonizes beta-catenin/TCF-mediated transcription. Carcinogenesis. 2010;31:394-401 pubmed publisher
    ..Our results show that EWS/FLI1 inhibits both DKK-1 expression as well as beta-catenin/TCF-dependent transcription, which could contribute to progression of tumours of the Ewing family. ..
  48. Cho K, Kim H, Kamanna V, Vaziri N. Niacin improves renal lipid metabolism and slows progression in chronic kidney disease. Biochim Biophys Acta. 2010;1800:6-15 pubmed publisher
    ..Present study sought to determine efficacy of niacin supplementation on renal tissue lipid metabolism in CRF...
  49. Stefansson H, Ophoff R, Steinberg S, Andreassen O, Cichon S, Rujescu D, et al. Common variants conferring risk of schizophrenia. Nature. 2009;460:744-7 pubmed publisher
    ..2. Our findings implicating the MHC region are consistent with an immune component to schizophrenia risk, whereas the association with NRGN and TCF4 points to perturbation of pathways involved in brain development, memory and cognition. ..
  50. Joo J, Kim Y, Dunn N, Sugrue S. Disruption of mouse corneal epithelial differentiation by conditional inactivation of pnn. Invest Ophthalmol Vis Sci. 2010;51:1927-34 pubmed publisher
    ..Conclusions. These data indicate that Pnn plays an essential role in modulating and/or orchestrating the activities of major developmental factors of anterior eye segments. ..
  51. Lee A, Glimcher L. Intersection of the unfolded protein response and hepatic lipid metabolism. Cell Mol Life Sci. 2009;66:2835-50 pubmed publisher
  52. Liu P, Yang J, Pei J, Pei D, Wilson M. Regulation of MT1-MMP activity by ?-catenin in MDCK non-cancer and HT1080 cancer cells. J Cell Physiol. 2010;225:810-21 pubmed publisher
    ..These differences were most probably due to different subcellular locations and different involved pathways of ?-catenin in these cells. ..
  53. Yamaguchi T, Kuroda N, Imamura Y, Hes O, Kawada T, Nakayama K. Imprint cytologic features in renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion in an adult: a case report. Acta Cytol. 2009;53:693-7 pubmed
    ..2 translocation/TFE3 gene fusion is suspected by imprint cytology even in adult-onset cases, and cytotechnologists should accurately recognize cytologic findings of this tumor. ..