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Gene Review

USF2  -  upstream transcription factor 2, c-fos...

Homo sapiens

Synonyms: BHLHB12, Class B basic helix-loop-helix protein 12, FIP, FOS-interacting protein, Major late transcription factor 2, ...
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Disease relevance of USF2


Psychiatry related information on USF2


High impact information on USF2

  • While the effect of USF1 was selective for Myc-dependent transformation, wild-type USF2 exerted in addition a strong inhibition of E1A-mediated transformation and a strong suppression of HeLa cell colony formation [7].
  • Both USF1 and USF2 inhibited the transformation of rat embryo fibroblasts mediated by Ras and c-Myc, a bHLH-zip transcription factor that also binds CACGTG motifs [7].
  • The USF1 and USF2 proteins contain highly divergent transcriptional activation domains but share extensive homologies in the bHLH-zip region and recognize the same CACGTG DNA motifs [7].
  • Whereas USF1 contained only an extended activation domain, USF2 contained both an activation domain and a negative regulatory region [8].
  • USF1 and USF2 are basic helix-loop-helix transcription factors implicated in the control of cellular proliferation [9].

Chemical compound and disease context of USF2

  • An immunohistochemical study of 108 formalin-fixed and paraffin-embedded human samples was undertaken to localize USF-2 expression and included 44 small cell and 32 non-small cell lung cancers, and 32 samples with bronchial dysplasia [10].
  • Although widely expressed, they can mediate tissue-specific transcription and we previously reported that USF-2 can enhance transcription of arginine vasopressin, a neuropeptide growth factor in small cell lung cancer [10].

Biological context of USF2

  • Recombinant USF1/USF2 binds to the RBEIII core sequence 160-fold less efficiently than it binds to an E box element, but the interaction with RBEIII is stimulated by TFII-I [11].
  • Based on the recent cloning of rat and human new cDNAs, we have isolated genomic clones encompassing the murine USF2 gene, which consists of at least 10 exons spanning a minimum of 10 kb of genomic DNA [12].
  • Unexpectedly, the organization of USF2 appears very split up by introns (0.08 to over 6 kb in size), compared to the myc gene structure [12].
  • USF1 and USF2 also lacked transcriptional activity in Saos-2 cells when assayed by transient cotransfection with USF-dependent reporter genes [9].
  • A particularly striking HpaII tiny fragment island, extending over nearly 2,000 base pairs, surrounds the USF2 translation initiation site [13].

Anatomical context of USF2


Associations of USF2 with chemical compounds

  • Overexpression of USF2 reversed the inhibitory effect of PKG on glucose-induced TSP1 gene transcription and TGF-beta activity [18].
  • We found that the E-box bound two factors, the USF1/USF2 protein and an unidentified ubiquitous protein which was named factor U [19].
  • Increasing O-GlcNAc modification of proteins by streptozotocin, thereby mimicking HBP activation, also resulted in increased mRNA and nuclear protein levels of USF-2, leading to enhanced DNA binding activity to the GlRE [20].
  • The high glucose-induced activation of the GlRE is mediated by the HBP; increased flux through the HBP induced by high glucose concentrations, by glutamine, or by overexpression of the rate-limiting enzyme glutamine:fructose-6-phosphate aminotransferase (GFAT) particularly activated USF-2 expression [20].
  • Finally, we present data showing that the suppressive effect of apigenin on COX-2 expression could be reversed by co-expression of USF-1 and USF-2 [21].

Physical interactions of USF2

  • Adenovirus-mediated overexpression of a dominant negative form of USF2 decreased binding of endogenous USF to the E-box element by approximately 90% [22].

Regulatory relationships of USF2


Other interactions of USF2

  • Through luciferase reporter assays, we found that both USF1 and USF2 possess a comparable effect on the inhibition of hTERT expression [27].
  • Here we show that RBF-2 is comprised of a USF1/USF2 heterodimer and TFII-I, which bind cooperatively to RBEIII [11].
  • Specifically, the N-terminally truncated form of USF2 is present in telomerase-negative/resting human lymphocytes, but not in telomerase-positive/phytohemagglutinin-activated lymphocytes [14].
  • However, USF2 did not stimulate hTOP3 alpha promoter activity in Saos-2 cells [15].
  • Moreover, HSL mRNA levels were decreased in USF1- and USF2-deficient mice [28].

Analytical, diagnostic and therapeutic context of USF2


  1. The IGF2 receptor is a USF2-specific target in nontumorigenic mammary epithelial cells but not in breast cancer cells. Szentirmay, M.N., Yang, H.X., Pawar, S.A., Vinson, C., Sawadogo, M. J. Biol. Chem. (2003) [Pubmed]
  2. USF/c-Myc enhances, while Yin-Yang 1 suppresses, the promoter activity of CXCR4, a coreceptor for HIV-1 entry. Moriuchi, M., Moriuchi, H., Margolis, D.M., Fauci, A.S. J. Immunol. (1999) [Pubmed]
  3. Down-regulation of the polymeric immunoglobulin receptor in non-small cell lung carcinoma: correlation with dysregulated expression of the transcription factors USF and AP2. Khattar, N.H., Lele, S.M., Kaetzel, C.S. J. Biomed. Sci. (2005) [Pubmed]
  4. Isolation of a novel USF2 isoform: repressor of cathepsin B expression. Yan, S., Sloane, B.F. Gene (2004) [Pubmed]
  5. Functional domains of the transcription factor USF2: atypical nuclear localization signals and context-dependent transcriptional activation domains. Luo, X., Sawadogo, M. Mol. Cell. Biol. (1996) [Pubmed]
  6. Genetic association between USF 1 and USF 2 gene polymorphisms and Japanese Alzheimer's disease. Shibata, N., Ohnuma, T., Higashi, S., Higashi, M., Usui, C., Ohkubo, T., Watanabe, T., Kawashima, R., Kitajima, A., Ueki, A., Nagao, M., Arai, H. J. Gerontol. A Biol. Sci. Med. Sci. (2006) [Pubmed]
  7. Antiproliferative properties of the USF family of helix-loop-helix transcription factors. Luo, X., Sawadogo, M. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  8. Upstream stimulatory factor regulates major histocompatibility complex class I gene expression: the U2DeltaE4 splice variant abrogates E-box activity. Howcroft, T.K., Murphy, C., Weissman, J.D., Huber, S.J., Sawadogo, M., Singer, D.S. Mol. Cell. Biol. (1999) [Pubmed]
  9. Cell-type-dependent activity of the ubiquitous transcription factor USF in cellular proliferation and transcriptional activation. Qyang, Y., Luo, X., Lu, T., Ismail, P.M., Krylov, D., Vinson, C., Sawadogo, M. Mol. Cell. Biol. (1999) [Pubmed]
  10. Roles for USF-2 in lung cancer proliferation and bronchial carcinogenesis. Ocejo-Garcia, M., Baokbah, T.A., Ashurst, H.L., Cowlishaw, D., Soomro, I., Coulson, J.M., Woll, P.J. J. Pathol. (2005) [Pubmed]
  11. TFII-I regulates induction of chromosomally integrated human immunodeficiency virus type 1 long terminal repeat in cooperation with USF. Chen, J., Malcolm, T., Estable, M.C., Roeder, R.G., Sadowski, I. J. Virol. (2005) [Pubmed]
  12. Structure, sequence, and chromosomal location of the gene for USF2 transcription factors in mouse. Henrion, A.A., Martinez, A., Mattei, M.G., Kahn, A., Raymondjean, M. Genomics (1995) [Pubmed]
  13. Archaic structure of the gene encoding transcription factor USF. Lin, Q., Luo, X., Sawadogo, M. J. Biol. Chem. (1994) [Pubmed]
  14. Variant forms of upstream stimulatory factors (USFs) control the promoter activity of hTERT, the human gene encoding the catalytic subunit of telomerase. Yago, M., Ohki, R., Hatakeyama, S., Fujita, T., Ishikawa, F. FEBS Lett. (2002) [Pubmed]
  15. Cell type-dependent regulation of human DNA topoisomerase III alpha gene expression by upstream stimulatory factor 2. Han, S.Y., Kim, J.C., Suh, J.M., Chung, I.K. FEBS Lett. (2001) [Pubmed]
  16. Transcription of the transforming growth factor-beta2 gene is dependent on an E-box located between an essential cAMP response element/activating transcription factor motif and the TATA box of the gene. Scholtz, B., Kingsley-Kallesen, M., Rizzino, A. J. Biol. Chem. (1996) [Pubmed]
  17. Loss of USF transcriptional activity in breast cancer cell lines. Ismail, P.M., Lu, T., Sawadogo, M. Oncogene (1999) [Pubmed]
  18. Glucose up-regulates thrombospondin 1 gene transcription and transforming growth factor-beta activity through antagonism of cGMP-dependent protein kinase repression via upstream stimulatory factor 2. Wang, S., Skorczewski, J., Feng, X., Mei, L., Murphy-Ullrich, J.E. J. Biol. Chem. (2004) [Pubmed]
  19. The E-box of the human glycophorin B promoter is involved in the erythroid-specific expression of the GPB gene. Camara-Clayette, V., Rahuel, C., Bertrand, O., Cartron, J.P. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  20. Upstream stimulatory factor (USF) proteins induce human TGF-beta1 gene activation via the glucose-response element-1013/-1002 in mesangial cells: up-regulation of USF activity by the hexosamine biosynthetic pathway. Weigert, C., Brodbeck, K., Sawadogo, M., Häring, H.U., Schleicher, E.D. J. Biol. Chem. (2004) [Pubmed]
  21. Modulation of UVB-induced and basal cyclooxygenase-2 (COX-2) expression by apigenin in mouse keratinocytes: Role of USF transcription factors. Van Dross, R.T., Hong, X., Essengue, S., Fischer, S.M., Pelling, J.C. Mol. Carcinog. (2007) [Pubmed]
  22. Upstream stimulatory factor regulates Pdx-1 gene expression in differentiated pancreatic beta-cells. Qian, J., Kaytor, E.N., Towle, H.C., Olson, L.K. Biochem. J. (1999) [Pubmed]
  23. Human papillomavirus type 16 E6 activates TERT gene transcription through induction of c-Myc and release of USF-mediated repression. McMurray, H.R., McCance, D.J. J. Virol. (2003) [Pubmed]
  24. Human follicle-stimulating hormone receptor (FSH-R) promoter/enhancer activity is inhibited by transcriptional factors, from the upstream stimulating factors family, via E-box and newly identified initiator element (Inr) in FSH-R non-expressing cells. Putowski, L.T., Schillings, W.J., Lee, C.M., Reddy, E.P., Jakowicki, J.A. Gynecol. Endocrinol. (2004) [Pubmed]
  25. Cell type-dependent regulation of the hypoxia-responsive plasminogen activator inhibitor-1 gene by upstream stimulatory factor-2. Dimova, E.Y., Kietzmann, T. J. Biol. Chem. (2006) [Pubmed]
  26. Upstream stimulatory factor 2 activates the mammalian F1F0 ATP synthase alpha-subunit gene through an initiator element. Breen, G.A., Jordan, E.M. Gene Expr. (1998) [Pubmed]
  27. Upstream stimulatory factor (USF) as a transcriptional suppressor of human telomerase reverse transcriptase (hTERT) in oral cancer cells. Chang, J.T., Yang, H.T., Wang, T.C., Cheng, A.J. Mol. Carcinog. (2005) [Pubmed]
  28. Transcriptional regulation of adipocyte hormone-sensitive lipase by glucose. Smih, F., Rouet, P., Lucas, S., Mairal, A., Sengenes, C., Lafontan, M., Vaulont, S., Casado, M., Langin, D. Diabetes (2002) [Pubmed]
  29. Immunochemical characterization and transacting properties of upstream stimulatory factor isoforms. Viollet, B., Lefrançois-Martinez, A.M., Henrion, A., Kahn, A., Raymondjean, M., Martinez, A. J. Biol. Chem. (1996) [Pubmed]
  30. Upstream stimulatory factor but not c-Myc enhances transcription of the human polymeric immunoglobulin receptor gene. Bruno, M.E., West, R.B., Schneeman, T.A., Bresnick, E.H., Kaetzel, C.S. Mol. Immunol. (2004) [Pubmed]
  31. Upstream stimulatory factor represses the induction of carnitine palmitoyltransferase-Ibeta expression by PGC-1. Moore, M.L., Park, E.A., McMillin, J.B. J. Biol. Chem. (2003) [Pubmed]
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