The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

GDF15  -  growth differentiation factor 15

Homo sapiens

Synonyms: GDF-15, Growth/differentiation factor 15, MIC-1, MIC1, Macrophage inhibitory cytokine 1, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of GDF15


Psychiatry related information on GDF15

  • Pigment-dispersing factor (PDF), an 18-amino acid neuropeptide, is a principal circadian neuromodulator functioning downstream of the insect brain's circadian clock, modulating daily rhythms of locomotor activity [8].

High impact information on GDF15


Chemical compound and disease context of GDF15


Biological context of GDF15

  • Growth differentiation factor (GDF15) is a distant member of the transforming growth factor-beta superfamily, a diverse group of structurally related proteins that exert multiple effects on cell fate such as on cell growth and differentiation but little is known about GDF15 in these processes [18].
  • NAG-1 (nonsteroidal anti-inflammatory drug-activated gene), a member of the transforming growth factor beta superfamily, is involved in cellular processes such as inflammation, apoptosis/survival, and tumorigenesis and is regulated by p53, Sp1, and Egr-1 [19].
  • The macrophage inhibitory cytokine-1 (MIC-1) gene was identified as a most prominent p53 target gene upon gene expression profiling [1].
  • Importantly, forced PDF expression in PC-3 cells results in decreased cell proliferation, soft agar cloning, and xenograft tumor size [20].
  • METHODS: Transient or stable expression of PDF by cDNA transfection, antisense-mediated gene silencing, media conditioned by PDF-elevated cells, and antibody (Ab) neutralization were employed [2].

Anatomical context of GDF15


Associations of GDF15 with chemical compounds

  • Furthermore, the mixture of I3C with resveratrol enhances NAG-1 expression, suggesting the synergistic effect of these two unrelated compounds on NAG-1 expression [3].
  • Indole-3-carbinol and 3,3'-diindolylmethane induce expression of NAG-1 in a p53-independent manner [3].
  • The dramatic increase of the nonsteroidal anti-inflammatory drug-activated gene 1 (NAG-1) made this gene an interesting candidate regarding the possible mechanism by which prodigiosin induces cytotoxicity in MCF-7 cells [4].
  • Growth and Differentiation Factor-15 (GDF-15, NAG-1, MIC-1) is induced by several apoptosis-inducing agents including the retinoid-related molecule (RRM) 6-[3-(1-adamantyl-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) [5].
  • Several RRMs (CD437, ST1926 and MX3350-1) but not the retinoids all-trans- retinoic acid and 4HPR were able to induce GDF-15 in H460 cells [5].

Physical interactions of GDF15


Regulatory relationships of GDF15

  • These results demonstrate that NAG-1 expression is up-regulated by TPA in LNCaP cells through a PKC-dependent pathway involving the activation of NF-kappa B [19].
  • CONCLUSION: PDF promotes AR-positive prostate tumor progression through upregulating cell proliferation via ERK1/2 signal pathway [2].
  • In this report, we show that the expression of the antitumorigenic and/or pro-apoptotic gene NAG-1 (nonsteroidal anti-inflammatory drug-activated gene-1) is induced by TGZ and correlates with EGR-1 induction [24].
  • In contrast to carcinoma cells, NAG-1 expression is effectively induced by retinoic acid and the RAR-selective pan-agonist in normal HTBE cells and accompanies the inhibition of squamous differentiation and the initiation of normal differentiation [12].
  • GDF15 is not expressed in the normal adult heart but is induced in response to conditions that promote hypertrophy and dilated cardiomyopathy [26].

Other interactions of GDF15

  • Expression of constitutively active PKCs induced an increase in NF-kappa B transcriptional activity and NAG-1 protein levels in LNCaP cells [19].
  • Nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1) is a TGF-beta superfamily gene associated with pro-apoptotic and anti-tumorigenic activities [3].
  • Expression of NAG-1, a transforming growth factor-beta superfamily member, by troglitazone requires the early growth response gene EGR-1 [24].
  • Furthermore, we provide evidence that ECG induces the ATF3 transcription factor, followed by NAG-1 induction at the transcriptional level in a p53-independent manner [15].
  • In contrast, other catechins do not significantly induce NAG-1 expression, PARP cleavage or morphological changes at up to a 50-microM concentration [15].

Analytical, diagnostic and therapeutic context of GDF15


  1. Anoxia induces macrophage inhibitory cytokine-1 (MIC-1) in glioblastoma cells independently of p53 and HIF-1. Albertoni, M., Shaw, P.H., Nozaki, M., Godard, S., Tenan, M., Hamou, M.F., Fairlie, D.W., Breit, S.N., Paralkar, V.M., de Tribolet, N., Van Meir, E.G., Hegi, M.E. Oncogene (2002) [Pubmed]
  2. Prostate-derived factor as a paracrine and autocrine factor for the proliferation of androgen receptor-positive human prostate cancer cells. Chen, S.J., Karan, D., Johansson, S.L., Lin, F.F., Zeckser, J., Singh, A.P., Batra, S.K., Lin, M.F. Prostate (2007) [Pubmed]
  3. Indole-3-carbinol and 3,3'-diindolylmethane induce expression of NAG-1 in a p53-independent manner. Lee, S.H., Kim, J.S., Yamaguchi, K., Eling, T.E., Baek, S.J. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  4. Prodigiosin induces the proapoptotic gene NAG-1 via glycogen synthase kinase-3beta activity in human breast cancer cells. Soto-Cerrato, V., Viñals, F., Lambert, J.R., Kelly, J.A., Pérez-Tomás, R. Mol. Cancer Ther. (2007) [Pubmed]
  5. Induction of GDF-15/NAG-1/MIC-1 in human lung carcinoma cells by retinoid-related molecules and assessment of its role in apoptosis. Kadara, H., Schroeder, C.P., Lotan, D., Pisano, C., Lotan, R. Cancer Biol. Ther. (2006) [Pubmed]
  6. Nonsteroidal anti-inflammatory drug-activated gene (NAG-1/GDF15) expression is increased by the histone deacetylase inhibitor trichostatin A. Yoshioka, H., Kamitani, H., Watanabe, T., Eling, T.E. J. Biol. Chem. (2008) [Pubmed]
  7. Macrophage inhibitory cytokine 1: a new prognostic marker in prostate cancer. Brown, D.A., Lindmark, F., Stattin, P., Bälter, K., Adami, H.O., Zheng, S.L., Xu, J., Isaacs, W.B., Grönberg, H., Breit, S.N., Wiklund, F.E. Clin. Cancer Res. (2009) [Pubmed]
  8. A circadian neuropeptide, pigment-dispersing factor-PDF, in the last-summer cicada Meimuna opalifera: cDNA cloning and immunocytochemistry. Sato, S., Chuman, Y., Matsushima, A., Tominaga, Y., Shimohigashi, Y., Shimohigashi, M. Zool. Sci. (2002) [Pubmed]
  9. Inhibition of TGF-beta 3 restores the invasive capability of extravillous trophoblasts in preeclamptic pregnancies. Caniggia, I., Grisaru-Gravnosky, S., Kuliszewsky, M., Post, M., Lye, S.J. J. Clin. Invest. (1999) [Pubmed]
  10. NAG-1/GDF-15: No Evidence for an Inhibitory Role in Colon Cancer? Zimmers, T.A., Gutierrez, J.C., Koniaris, L.G. Gastroenterology (2007) [Pubmed]
  11. Nonsteroidal anti-inflammatory drug-activated gene-1 over expression in transgenic mice suppresses intestinal neoplasia. Baek, S.J., Okazaki, R., Lee, S.H., Martinez, J., Kim, J.S., Yamaguchi, K., Mishina, Y., Martin, D.W., Shoieb, A., McEntee, M.F., Eling, T.E. Gastroenterology (2006) [Pubmed]
  12. Differential regulation of nonsteroidal anti-inflammatory drug-activated gene in normal human tracheobronchial epithelial and lung carcinoma cells by retinoids. Newman, D., Sakaue, M., Koo, J.S., Kim, K.S., Baek, S.J., Eling, T., Jetten, A.M. Mol. Pharmacol. (2003) [Pubmed]
  13. 1,1-Bis(3'-indolyl)-1-(p-substitutedphenyl)methanes are peroxisome proliferator-activated receptor gamma agonists but decrease HCT-116 colon cancer cell survival through receptor-independent activation of early growth response-1 and nonsteroidal anti-inflammatory drug-activated gene-1. Chintharlapalli, S., Papineni, S., Baek, S.J., Liu, S., Safe, S. Mol. Pharmacol. (2005) [Pubmed]
  14. Nonsteroidal anti-inflammatory drug-activated gene (NAG-1) is induced by genistein through the expression of p53 in colorectal cancer cells. Wilson, L.C., Baek, S.J., Call, A., Eling, T.E. Int. J. Cancer (2003) [Pubmed]
  15. Epicatechin gallate-induced expression of NAG-1 is associated with growth inhibition and apoptosis in colon cancer cells. Baek, S.J., Kim, J.S., Jackson, F.R., Eling, T.E., McEntee, M.F., Lee, S.H. Carcinogenesis (2004) [Pubmed]
  16. Macrophage inhibitory cytokine-1: a novel biomarker for p53 pathway activation. Yang, H., Filipovic, Z., Brown, D., Breit, S.N., Vassilev, L.T. Mol. Cancer Ther. (2003) [Pubmed]
  17. Molecular alterations in prostate carcinomas that associate with in vivo exposure to chemotherapy: identification of a cytoprotective mechanism involving growth differentiation factor 15. Huang, C.Y., Beer, T.M., Higano, C.S., True, L.D., Vessella, R., Lange, P.H., Garzotto, M., Nelson, P.S. Clin. Cancer Res. (2007) [Pubmed]
  18. Dynamics of expression of growth differentiation factor 15 in normal and PIN development in the mouse. Noorali, S., Kurita, T., Woolcock, B., de Algara, T.R., Lo, M., Paralkar, V., Hoodless, P., Vielkind, J. Differentiation (2007) [Pubmed]
  19. Protein kinase C-dependent regulation of NAG-1/placental bone morphogenic protein/MIC-1 expression in LNCaP prostate carcinoma cells. Shim, M., Eling, T.E. J. Biol. Chem. (2005) [Pubmed]
  20. Prostate derived factor in human prostate cancer cells: gene induction by vitamin D via a p53-dependent mechanism and inhibition of prostate cancer cell growth. Lambert, J.R., Kelly, J.A., Shim, M., Huffer, W.E., Nordeen, S.K., Baek, S.J., Eling, T.E., Lucia, M.S. J. Cell. Physiol. (2006) [Pubmed]
  21. The propeptide of macrophage inhibitory cytokine (MIC-1), a TGF-beta superfamily member, acts as a quality control determinant for correctly folded MIC-1. Bauskin, A.R., Zhang, H.P., Fairlie, W.D., He, X.Y., Russell, P.K., Moore, A.G., Brown, D.A., Stanley, K.K., Breit, S.N. EMBO J. (2000) [Pubmed]
  22. Macrophage inhibitory cytokine 1 mediates a p53-dependent protective arrest in S phase in response to starvation for DNA precursors. Agarwal, M.K., Hastak, K., Jackson, M.W., Breit, S.N., Stark, G.R., Agarwal, M.L. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  23. MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-beta superfamily. Bootcov, M.R., Bauskin, A.R., Valenzuela, S.M., Moore, A.G., Bansal, M., He, X.Y., Zhang, H.P., Donnellan, M., Mahler, S., Pryor, K., Walsh, B.J., Nicholson, R.C., Fairlie, W.D., Por, S.B., Robbins, J.M., Breit, S.N. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  24. Expression of NAG-1, a transforming growth factor-beta superfamily member, by troglitazone requires the early growth response gene EGR-1. Baek, S.J., Kim, J.S., Nixon, J.B., DiAugustine, R.P., Eling, T.E. J. Biol. Chem. (2004) [Pubmed]
  25. Resveratrol enhances the expression of non-steroidal anti-inflammatory drug-activated gene (NAG-1) by increasing the expression of p53. Baek, S.J., Wilson, L.C., Eling, T.E. Carcinogenesis (2002) [Pubmed]
  26. GDF15/MIC-1 functions as a protective and antihypertrophic factor released from the myocardium in association with SMAD protein activation. Xu, J., Kimball, T.R., Lorenz, J.N., Brown, D.A., Bauskin, A.R., Klevitsky, R., Hewett, T.E., Breit, S.N., Molkentin, J.D. Circ. Res. (2006) [Pubmed]
  27. Circulating concentrations of growth-differentiation factor 15 in apparently healthy elderly individuals and patients with chronic heart failure as assessed by a new immunoradiometric sandwich assay. Kempf, T., Horn-Wichmann, R., Brabant, G., Peter, T., Allhoff, T., Klein, G., Drexler, H., Johnston, N., Wallentin, L., Wollert, K.C. Clin. Chem. (2007) [Pubmed]
  28. Concentration in plasma of macrophage inhibitory cytokine-1 and risk of cardiovascular events in women: a nested case-control study. Brown, D.A., Breit, S.N., Buring, J., Fairlie, W.D., Bauskin, A.R., Liu, T., Ridker, P.M. Lancet (2002) [Pubmed]
  29. Macrophage inhibitory cytokine 1 reduces cell adhesion and induces apoptosis in prostate cancer cells. Liu, T., Bauskin, A.R., Zaunders, J., Brown, D.A., Pankhurst, S., Russell, P.J., Breit, S.N., Panhurst, S. Cancer Res. (2003) [Pubmed]
  30. Cloning and characterization of a novel member of the transforming growth factor-beta/bone morphogenetic protein family. Paralkar, V.M., Vail, A.L., Grasser, W.A., Brown, T.A., Xu, H., Vukicevic, S., Ke, H.Z., Qi, H., Owen, T.A., Thompson, D.D. J. Biol. Chem. (1998) [Pubmed]
  31. Molecular cloning and characterization of human nonsteroidal anti-inflammatory drug-activated gene promoter. Basal transcription is mediated by Sp1 and Sp3. Baek, S.J., Horowitz, J.M., Eling, T.E. J. Biol. Chem. (2001) [Pubmed]
WikiGenes - Universities