sp transcription factors


Summary: A family of DNA-binding proteins that contain three ZINC FINGERS at their carboxy termini. They are transcription factors that have specificity for GC boxes.

Top Publications

  1. Chintharlapalli S, Papineni S, Lei P, Pathi S, Safe S. Betulinic acid inhibits colon cancer cell and tumor growth and induces proteasome-dependent and -independent downregulation of specificity proteins (Sp) transcription factors. BMC Cancer. 2011;11:371 pubmed publisher
    ..These results suggest that the anticancer activity of BA in colon cancer cells is due, in part, to downregulation of Sp1, Sp3 and Sp4 transcription factors; however, the mechanism of this response is cell context-dependent. ..
  2. Wu F, Ivanov I, Xu R, Safe S. Role of SP transcription factors in hormone-dependent modulation of genes in MCF-7 breast cancer cells: microarray and RNA interference studies. J Mol Endocrinol. 2009;42:19-33 pubmed publisher
    ..protein (SP) transcription factors is a nonclassical genomic estrogenic pathway and the role of SP transcription factors in mediating hormone-dependent activation or repression of genes in MCF-7 cells was investigated by ..
  3. Abdelrahim M, Baker C, Abbruzzese J, Sheikh Hamad D, Liu S, Cho S, et al. Regulation of vascular endothelial growth factor receptor-1 expression by specificity proteins 1, 3, and 4 in pancreatic cancer cells. Cancer Res. 2007;67:3286-94 pubmed
    ..Thus, targeted degradation of Sp proteins is highly effective for inhibiting VEGFR1 and associated angiogenic responses in pancreatic cancer. ..
  4. Abdelrahim M, Baker C, Abbruzzese J, Safe S. Tolfenamic acid and pancreatic cancer growth, angiogenesis, and Sp protein degradation. J Natl Cancer Inst. 2006;98:855-68 pubmed
    ..009) than tumors from control mice. Tolfenamic acid is a new antipancreatic cancer NSAID that activates degradation of transcription factors Sp1, Sp3, and Sp4; reduces VEGF expression; and decreases tumor growth and metastasis. ..
  5. Jutooru I, Chadalapaka G, Sreevalsan S, Lei P, Barhoumi R, Burghardt R, et al. Arsenic trioxide downregulates specificity protein (Sp) transcription factors and inhibits bladder cancer cell and tumor growth. Exp Cell Res. 2010;316:2174-88 pubmed publisher
  6. Safe S, Abdelrahim M. Sp transcription factor family and its role in cancer. Eur J Cancer. 2005;41:2438-48 pubmed
    ..Sp/KLF proteins are also potential targets for cancer chemotherapy. ..
  7. Chintharlapalli S, Papineni S, Abdelrahim M, Abudayyeh A, Jutooru I, Chadalapaka G, et al. Oncogenic microRNA-27a is a target for anticancer agent methyl 2-cyano-3,11-dioxo-18beta-olean-1,12-dien-30-oate in colon cancer cells. Int J Cancer. 2009;125:1965-74 pubmed publisher
    ..Both CDODA-Me and antisense miR-27a induced comparable responses in RKO and SW480 cells, suggesting that the potent anticarcinogenic activity of CDODA-Me is due to repression of oncogenic miR-27a. ..
  8. Mertens Talcott S, Noratto G, Li X, Angel Morales G, Bertoldi M, Safe S. Betulinic acid decreases ER-negative breast cancer cell growth in vitro and in vivo: role of Sp transcription factors and microRNA-27a:ZBTB10. Mol Carcinog. 2013;52:591-602 pubmed publisher
    ..These results show that the anticancer effects of BA are at least in part based on interactions with the microRNA-27a-ZBTB10-Sp-axis causing increased cell death. ..
  9. Malek A, Núñez L, Magistri M, Brambilla L, Jovic S, Carbone G, et al. Modulation of the activity of Sp transcription factors by mithramycin analogues as a new strategy for treatment of metastatic prostate cancer. PLoS ONE. 2012;7:e35130 pubmed publisher
    ..Taken together, these data indicate that MTM-SDK and MTM-SK possess significantly improved pharmacological and toxicological properties compared to MTM-A and represent promising drugs for treatment of advanced prostate cancer. ..

More Information


  1. Tapias A, Ciudad C, Noe V. Transcriptional regulation of the 5'-flanking region of the human transcription factor Sp3 gene by NF-1, c-Myb, B-Myb, AP-1 and E2F. Biochim Biophys Acta. 2008;1779:318-29 pubmed publisher
    ..These results help to explain the complex regulation of the Sp3 gene, which depends, at least in part, on the relative amount of Sp1, Sp3, NF-Y, NF-1, c-Myb, B-Myb, AP-1, and E2F proteins in the cell. ..
  2. Milagre I, Nunes M, Gama M, Silva R, Pascussi J, Lechner M, et al. Transcriptional regulation of the human CYP46A1 brain-specific expression by Sp transcription factors. J Neurochem. 2008;106:835-49 pubmed publisher
    ..Our results suggest that the cell-type specific expression of Sp transcription factors - substitution of Sp1 by Sp4 in neurons - is responsible for the basal expression of the CYP46A1 gene...
  3. Chadalapaka G, Jutooru I, Burghardt R, Safe S. Drugs that target specificity proteins downregulate epidermal growth factor receptor in bladder cancer cells. Mol Cancer Res. 2010;8:739-50 pubmed publisher
    ..Thus, compounds such as curcumin and BA that downregulate Sp transcription factors represent a novel class of anticancer drugs that target EGFR in bladder cancer cells and tumors by ..
  4. Milagre I, Nunes M, Castro Caldas M, Moutinho M, Gama M, Rodrigues E. Neuronal differentiation alters the ratio of Sp transcription factors recruited to the CYP46A1 promoter. J Neurochem. 2012;120:220-9 pubmed publisher
    ..Our data indicate that the dissociation of Sp1 from promoter regions is a common feature amongst Sp-regulated genes that are up-regulated after neuronal differentiation. ..
  5. Chadalapaka G, Jutooru I, Safe S. Celastrol decreases specificity proteins (Sp) and fibroblast growth factor receptor-3 (FGFR3) in bladder cancer cells. Carcinogenesis. 2012;33:886-94 pubmed publisher
    ..Thus, the anticancer activity of CSL in 253JB-V cells is due to induction of ROS and ROS-mediated induction of Sp repressors (ZBTB4/ZBTB10) through downregulation of miR-27a and miR-20a/17-5p. ..
  6. Pathi S, Jutooru I, Chadalapaka G, Sreevalsan S, Anand S, Thatcher G, et al. GT-094, a NO-NSAID, inhibits colon cancer cell growth by activation of a reactive oxygen species-microRNA-27a: ZBTB10-specificity protein pathway. Mol Cancer Res. 2011;9:195-202 pubmed publisher
  7. Papineni S, Chintharlapalli S, Abdelrahim M, Lee S, Burghardt R, Abudayyeh A, et al. Tolfenamic acid inhibits esophageal cancer through repression of specificity proteins and c-Met. Carcinogenesis. 2009;30:1193-201 pubmed publisher
    ..Thus, TA-dependent downregulation of Sp transcription factors and c-Met defines a novel chemotherapeutic approach for treatment of esophageal cancer.
  8. Small K, Hedman A, Grundberg E, Nica A, Thorleifsson G, Kong A, et al. Identification of an imprinted master trans regulator at the KLF14 locus related to multiple metabolic phenotypes. Nat Genet. 2011;43:561-4 pubmed publisher
    ..This trans-eQTL network provides a mechanistic understanding of the effect of the KLF14 locus on metabolic disease risk and offers a potential model for other complex traits. ..
  9. Chadalapaka G, Jutooru I, Chintharlapalli S, Papineni S, Smith R, Li X, et al. Curcumin decreases specificity protein expression in bladder cancer cells. Cancer Res. 2008;68:5345-54 pubmed publisher
    ..These results show for the first time that one of the underlying mechanisms of action of curcumin as a cancer chemotherapeutic agent is due, in part, to decreased expression of Sp transcription factors in bladder cancer cells.
  10. Chen X, Li S, Yang Y, Yang X, Liu Y, Hu W, et al. Genome-wide association study validation identifies novel loci for atherosclerotic cardiovascular disease. J Thromb Haemost. 2012;10:1508-14 pubmed publisher
    ..In addition, we found that a missense variant of KLF14, rs111400400 (Ser58Pro), was associated with MI. Genetic variants newly identified near/in the KLF14 gene were implicated in the aetiology of atherosclerotic-related phenotypes. ..
  11. Kim K, Chadalapaka G, Lee S, Yamada D, Sastre Garau X, Defossez P, et al. Identification of oncogenic microRNA-17-92/ZBTB4/specificity protein axis in breast cancer. Oncogene. 2012;31:1034-44 pubmed publisher
    ..downregulation of several Sp-dependent oncogenes, in part, through competition between ZBTB4 and Sp transcription factors for GC-rich promoter sequences...
  12. Jutooru I, Chadalapaka G, Lei P, Safe S. Inhibition of NFkappaB and pancreatic cancer cell and tumor growth by curcumin is dependent on specificity protein down-regulation. J Biol Chem. 2010;285:25332-44 pubmed publisher
    ..Because both Sp transcription factors and NFkappaB regulate several common genes such as cyclin D1, survivin, and vascular endothelial growth ..
  13. Yokoyama K, Pollock D. SP transcription factor paralogs and DNA-binding sites coevolve and adaptively converge in mammals and birds. Genome Biol Evol. 2012;4:1102-17 pubmed publisher
    ..Thus, multiple lines of evidence indicate that selection has driven convergent evolution of transcription factors along with their binding sites and coregulatory proteins...
  14. Fernandez Zapico M, Lomberk G, Tsuji S, DeMars C, Bardsley M, Lin Y, et al. A functional family-wide screening of SP/KLF proteins identifies a subset of suppressors of KRAS-mediated cell growth. Biochem J. 2011;435:529-37 pubmed publisher
  15. Nair A, Piaggi P, McLean N, Kaur M, Kobes S, Knowler W, et al. Assessment of established HDL-C loci for association with HDL-C levels and type 2 diabetes in Pima Indians. Diabetologia. 2016;59:481-91 pubmed publisher
    ..However, since HNF4A and KLF14 are established loci for type 2 diabetes, it is unlikely that HDL-C solely mediates these associations. ..
  16. Huang P, Yin R, Huang K, Zeng X, Guo T, Lin Q, et al. Association of the KLF14 rs4731702 SNP and serum lipid levels in the Guangxi Mulao and Han populations. Biomed Res Int. 2013;2013:231515 pubmed publisher
    ..The differences in the association of KLF14 rs4731702 SNP and serum lipid levels between the two ethnic groups might partly result from different gene-environmental interactions. ..
  17. Hanson R, Guo T, Muller Y, Fleming J, Knowler W, Kobes S, et al. Strong parent-of-origin effects in the association of KCNQ1 variants with type 2 diabetes in American Indians. Diabetes. 2013;62:2984-91 pubmed publisher
    ..In Pima Indians, the effect of maternally derived KCNQ1 variants appears to be mediated through decreased insulin secretion and is particularly strong, accounting for 4% of the variance in liability to diabetes. ..
  18. Wilson H, Chadalapaka G, Jutooru I, Sheppard S, Pfent C, Safe S. Effect of tolfenamic acid on canine cancer cell proliferation, specificity protein (sp) transcription factors, and sp-regulated proteins in canine osteosarcoma, mammary carcinoma, and melanoma cells. J Vet Intern Med. 2012;26:977-86 pubmed publisher
    ..CONCLUSIONS, AND CLINICAL IMPORTANCE: Tolfenamic acid is a potential anticancer NSAID and further investigation is needed to determine its usefulness in a clinical setting. ..
  19. Leupold J, Asangani I, Mudduluru G, Allgayer H. Promoter cloning and characterization of the human programmed cell death protein 4 (pdcd4) gene: evidence for ZBP-89 and Sp-binding motifs as essential Pdcd4 regulators. Biosci Rep. 2012;32:281-97 pubmed publisher
    ..In contrast with Sp transcription factors, overexpression of ZBP-89 led to an enhanced expression of Pdcd4 mRNA and protein...
  20. Kim K, Chadalapaka G, Pathi S, Jin U, Lee J, Park Y, et al. Induction of the transcriptional repressor ZBTB4 in prostate cancer cells by drug-induced targeting of microRNA-17-92/106b-25 clusters. Mol Cancer Ther. 2012;11:1852-62 pubmed publisher
    ..potent inhibitor of tumor growth in a mouse xenograft model (PC3 cells) and also decreased expression of Sp transcription factors in tumors...
  21. Hu J, Navas P, Cao H, Stamatoyannopoulos G, Song C. Systematic RNAi studies on the role of Sp/KLF factors in globin gene expression and erythroid differentiation. J Mol Biol. 2007;366:1064-73 pubmed
    ..The expression of c-Kit, however, was significantly up-regulated. These data indicate that Sp1 may play an important role in erythroid differentiation. ..
  22. Sankpal U, Maliakal P, Bose D, Kayaleh O, Buchholz D, Basha R. Expression of specificity protein transcription factors in pancreatic cancer and their association in prognosis and therapy. Curr Med Chem. 2012;19:3779-86 pubmed
    ..curcumin, and tolfenamic acid has showed promising results in pre-clinical studies and demonstrated Sp transcription factors as potential targets for pancreatic cancer therapy...
  23. Suttamanatwong S, Jensen E, Schilling J, Franceschi R, Carlson A, Mansky K, et al. Sp proteins and Runx2 mediate regulation of matrix gla protein (MGP) expression by parathyroid hormone. J Cell Biochem. 2009;107:284-92 pubmed publisher
    ..Collectively, these data show that PTH regulates MGP gene transcription in osteoblasts through altered activities of Sp and Runx2 transcription factors. ..
  24. Xu K, Chang C, Gao H, Shu H. Epidermal growth factor-dependent cyclooxygenase-2 induction in gliomas requires protein kinase C-delta. Oncogene. 2009;28:1410-20 pubmed publisher
    ..These data provide the first evidence that PKC-delta is a critical link between p38-MAPK and Sp1-dependent COX-2 expression in human glioma cells. ..
  25. Gao K, Wang J, Li L, Zhai Y, Ren Y, You H, et al. Polymorphisms in Four Genes (KCNQ1 rs151290, KLF14 rs972283, GCKR rs780094 and MTNR1B rs10830963) and Their Correlation with Type 2 Diabetes Mellitus in Han Chinese in Henan Province, China. Int J Environ Res Public Health. 2016;13: pubmed publisher
    ..The AC and CC genotypes and the C allele of rs151290 in KCNQ1 may be risk factors for T2DM in Han Chinese in Henan province. ..
  26. Lee C, Lee Y, Lee J, Lee S, Ahn K. Nrf2 and Sp family synergistically enhance the expression of ion transporters in potassium-depleted conditions. J Nephrol. 2012;25:225-32 pubmed publisher
    ..These results suggest that Nrf2 mediates transcriptional activation of colonic H/K-ATPase and kNBC1 in response to K-depleted stress and augments Sp family-mediated expression of these ion transporters. ..
  27. Koutsodontis G, Vasilaki E, Chou W, Papakosta P, Kardassis D. Physical and functional interactions between members of the tumour suppressor p53 and the Sp families of transcription factors: importance for the regulation of genes involved in cell-cycle arrest and apoptosis. Biochem J. 2005;389:443-55 pubmed
    ..Understanding in detail how members of the p53 and Sp families of transcription factors interact and work together in the p53-mediated cellular responses may open new horizons in cancer chemotherapy. ..
  28. Nielsen T, Sparsø T, Grarup N, Jørgensen T, Pisinger C, Witte D, et al. Type 2 diabetes risk allele near CENTD2 is associated with decreased glucose-stimulated insulin release. Diabetologia. 2011;54:1052-6 pubmed publisher
  29. Mao X, Moerman Herzog A, Wang W, Barger S. Differential transcriptional control of the superoxide dismutase-2 kappaB element in neurons and astrocytes. J Biol Chem. 2006;281:35863-72 pubmed
  30. Bazhin A, Schadendorf D, Owen R, Zernii E, Philippov P, Eichmüller S. Visible light modulates the expression of cancer-retina antigens. Mol Cancer Res. 2008;6:110-8 pubmed publisher
    ..The visual cascade and retinoic acid as its derivate do not play any role in this process. Putative explanations for light-dependent modulation of cancer-retina antigen expression in melanoma cells are discussed. ..
  31. Luciakova K, Kollarovic G, Barath P, Nelson B. Growth-dependent repression of human adenine nucleotide translocator-2 (ANT2) transcription: evidence for the participation of Smad and Sp family proteins in the NF1-dependent repressor complex. Biochem J. 2008;412:123-30 pubmed publisher
    ..These findings suggest a possible functional relationship between the NF1 and Smad proteins that has not been previously observed. ..
  32. Truty M, Lomberk G, Fernandez Zapico M, Urrutia R. Silencing of the transforming growth factor-beta (TGFbeta) receptor II by Kruppel-like factor 14 underscores the importance of a negative feedback mechanism in TGFbeta signaling. J Biol Chem. 2009;284:6291-300 pubmed publisher
  33. Colon J, Basha M, Madero Visbal R, Konduri S, Baker C, Herrera L, et al. Tolfenamic acid decreases c-Met expression through Sp proteins degradation and inhibits lung cancer cells growth and tumor formation in orthotopic mice. Invest New Drugs. 2011;29:41-51 pubmed publisher
  34. Nunes M, Milagre I, Schnekenburger M, Gama M, Diederich M, Rodrigues E. Sp proteins play a critical role in histone deacetylase inhibitor-mediated derepression of CYP46A1 gene transcription. J Neurochem. 2010;113:418-31 pubmed publisher
    ..Silencing of Sp transcription factors through specific small interfering RNAs, or impairing Sp binding to the proximal promoter, by site-..
  35. Basha R, Baker C, Sankpal U, Ahmad S, Safe S, Abbruzzese J, et al. Therapeutic applications of NSAIDS in cancer: special emphasis on tolfenamic acid. Front Biosci (Schol Ed). 2011;3:797-805 pubmed
    ..In this review, we provide a summary on the potential benefits of NSAIDs in a variety of human cancers with more emphasis on tolfenamic acid. ..
  36. Cote Vélez A, Perez Maldonado A, Osuna J, Barrera B, Charli J, Joseph Bravo P. Creb and Sp/Krüppel response elements cooperate to control rat TRH gene transcription in response to cAMP. Biochim Biophys Acta. 2011;1809:191-9 pubmed publisher
  37. Basha R, Ingersoll S, Sankpal U, Ahmad S, Baker C, Edwards J, et al. Tolfenamic acid inhibits ovarian cancer cell growth and decreases the expression of c-Met and survivin through suppressing specificity protein transcription factors. Gynecol Oncol. 2011;122:163-70 pubmed publisher
    ..This study represents potential role(s) of TA that suppresses OC cell growth, and may enhance tumor response to radiotherapy, and have implications in OC treatment. ..
  38. Moorefield K, Yin H, Nichols T, Cathcart C, Simmons S, Horowitz J. Sp2 localizes to subnuclear foci associated with the nuclear matrix. Mol Biol Cell. 2006;17:1711-22 pubmed
    ..We conclude that Sp2 preferentially associates with the nuclear matrix and speculate that this subcellular localization plays an important role in the regulation of Sp2 function. ..
  39. Cho S, Jung S, Hong S, Lee E, Lee J, Lee S, et al. Independent validation of DNA-based approaches for age prediction in blood. Forensic Sci Int Genet. 2017;29:250-256 pubmed publisher
    ..Our study demonstrates the usefulness of the proposed markers and the genotyping method in an independent dataset, and suggests the possibility of combining different types of DNA markers to improve prediction accuracy. ..
  40. Scohy S, Gabant P, Van Reeth T, Hertveldt V, Dreze P, Van Vooren P, et al. Identification of KLF13 and KLF14 (SP6), novel members of the SP/XKLF transcription factor family. Genomics. 2000;70:93-101 pubmed
    ..3-q22 (human KLF14; HGMW-approved symbol SP6), and 2p25 (human KLF11) and chromosomes 1q31-q32 (rat Klf13), 10q31-q32.1 (rat Klf14) (SP6), and 6q16-q21 (rat Klf11). ..
  41. Xiao F, Mirwald A, Papaioannou M, Baniahmad A, Klug J. Secretoglobin 2A1 is under selective androgen control mediated by a peculiar binding site for Sp family transcription factors. Mol Endocrinol. 2005;19:2964-78 pubmed
    ..Therefore we propose that SCGB 2A1 represents a new class of androgen target genes that are purely under indirect AR control mediated by DNA-bound Sp factors. ..
  42. Dong L, Liu A, Wang J, Ma C, Zhu T, Yan X. [Effect of acupuncture of Ho (ST 36)-plus Mu (CV 12)-acupoints on hypothalamic gonadotropin-releasing hormone mRNA and SP mRNA expression in stress-induced gastric ulcer rats]. Zhen Ci Yan Jiu. 2013;38:291-6 pubmed
    ..05). Acupuncture of CV 12 and ST 36 can relieve stress-induced gastric ulcer in the rat, which is closely with its effect in down-regulating hypothalamic GnRH mRNA expression. ..
  43. Das S, Ward S, Tacke R, Suske G, Samuel C. Activation of the RNA-dependent protein kinase PKR promoter in the absence of interferon is dependent upon Sp proteins. J Biol Chem. 2006;281:3244-53 pubmed
    ..These results establish that, in the absence of IFN treatment, activation of PKR basal expression is mediated by Sp1 and Sp3 proteins in a cooperative manner. ..
  44. Gandhy S, Kim K, Larsen L, Rosengren R, Safe S. Curcumin and synthetic analogs induce reactive oxygen species and decreases specificity protein (Sp) transcription factors by targeting microRNAs. BMC Cancer. 2012;12:564 pubmed publisher
    ..The mechanism of curcumin-/RL197-induced repression of Sp transcription factors was ROS-dependent and due to induction of the Sp repressors ZBTB10 and ZBTB4 and downregulation of ..
  45. Pathi S, Jutooru I, Chadalapaka G, Nair V, Lee S, Safe S. Aspirin inhibits colon cancer cell and tumor growth and downregulates specificity protein (Sp) transcription factors. PLoS ONE. 2012;7:e48208 pubmed publisher
  46. Liu X, Jutooru I, Lei P, Kim K, Lee S, Brents L, et al. Betulinic acid targets YY1 and ErbB2 through cannabinoid receptor-dependent disruption of microRNA-27a:ZBTB10 in breast cancer. Mol Cancer Ther. 2012;11:1421-31 pubmed publisher
  47. Harris S, Harvey E, Hughes T, Ramji D. The interferon-gamma-mediated inhibition of lipoprotein lipase gene transcription in macrophages involves casein kinase 2- and phosphoinositide-3-kinase-mediated regulation of transcription factors Sp1 and Sp3. Cell Signal. 2008;20:2296-301 pubmed publisher
    ..Taken together, these results suggest a key role for CK2 and PI3K signalling pathways in the IFN-gamma-mediated inhibition of macrophage LPL gene transcription through the regulation of Sp1/Sp3 binding. ..
  48. Jiang W, Cui J, Xie D, Wang L. Sp/KLF family and tumor angiogenesis in pancreatic cancer. Curr Pharm Des. 2012;18:2420-31 pubmed
    ..Furthermore, it could also help to design effective strategies to target the key components of the network and control the development and progression of tumor. ..
  49. Staun Ram E, Goldman S, Shalev E. p53 Mediates epidermal growth factor (EGF) induction of MMP-2 transcription and trophoblast invasion. Placenta. 2009;30:1029-36 pubmed publisher
    ..p53 mediates both basic and EGF-induced MMP-2 transcription. ..
  50. Bihaqi S, Zawia N. Alzheimer's disease biomarkers and epigenetic intermediates following exposure to Pb in vitro. Curr Alzheimer Res. 2012;9:555-62 pubmed
    ..RT-PCR analysis of Dnmt1, Dnmt3a and MeCP2 indicated a significant down-regulation of the mRNA levels. These data suggest that Pb interferes with DNA methylating capacity in these cells, thus altering the expression of AD-related genes. ..
  51. Hekmatnejad B, Gauthier C, St Arnaud R. Control of Fiat (factor inhibiting ATF4-mediated transcription) expression by Sp family transcription factors in osteoblasts. J Cell Biochem. 2013;114:1863-70 pubmed publisher
    ..Taken together, our results suggest an interplay between Sp1 and Sp3 as a mechanism involved in the control of Fiat gene expression in osteoblasts...
  52. Wang J, Michelhaugh S, Bannon M. Valproate robustly increases Sp transcription factor-mediated expression of the dopamine transporter gene within dopamine cells. Eur J Neurosci. 2007;25:1982-6 pubmed
    ..In summary, valproate treatment significantly increased DAT gene expression in a Sp transcription factor-dependent manner. Some of valproate's therapeutic effects may involve activation of DAT gene expression. ..
  53. Canny G, Cario E, Lennartsson A, Gullberg U, Brennan C, Levy O, et al. Functional and biochemical characterization of epithelial bactericidal/permeability-increasing protein. Am J Physiol Gastrointest Liver Physiol. 2006;290:G557-67 pubmed
    ..Taken together, these data confirm the transcriptional regulation of BPI in intestinal epithelia and provide insight into the relevance of BPI as an anti-infective molecule at intestinal surfaces. ..