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Chemical Compound Review

Dermagan     N-ethanoyl-N-[2-methyl-4-(2...

Synonyms: Dermagen, Granulin, Pellidol, azodolen, Diamazo, ...
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Disease relevance of Diamazo

  • PC-cell derived growth factor (PCDGF) is an 88-kDa growth factor originally purified from the highly tumorigenic teratoma PC cell line and corresponds to the epithelin/granulin precursor [1].
  • We identified granulin as a cyclin T1-interacting protein that represses expression from the HIV-1 promoter in transfected cells [2].
  • The differential expression pattern, tissue distribution, and implication of this glioma-associated molecule in growth regulation suggest a potentially important role for granulin in the pathogenesis and/or malignant progression of primary brain neoplasms [3].
  • The current study found zinc associated with both granulosis virus nucleocapsids and granulin by atomic absorption analysis [4].
  • Substitution of granulin from the Trichoplusia ni granulosis virus (TnGV) for polyhedrin of the Autographa californica multinucleocapsid nuclear polyhedrosis virus (AcMNPV) yielded a few very large (2 to 5 micron) cuboidal inclusions in the cytoplasm and nucleus of infected cells [5].

High impact information on Diamazo

  • Inhibition of PC cell-derived growth factor (PCDGF, epithelin/granulin precursor) expression by antisense PCDGF cDNA transfection inhibits tumorigenicity of the human breast carcinoma cell line MDA-MB-468 [1].
  • The granulin/epithelin protein motif has an unusual structure consisting of a parallel stack of beta-hairpins stapled together by six disulphide bonds [6].
  • Epithelin 1, which is probably identical to rat leukocyte granulin, exhibits proliferative and antiproliferative effects on epithelial cells in vitro [7].
  • Isolation and sequence of the granulin precursor cDNA from human bone marrow reveals tandem cysteine-rich granulin domains [7].
  • The growth factor granulin interacts with cyclin T1 and modulates P-TEFb-dependent transcription [2].

Chemical compound and disease context of Diamazo

  • Using in vitro mutagenesis assays, we showed that each one of the three cysteine residues located within the cysteine-rich domain of the CAEV Tat protein is essential for the binding of Tat to both the Notch2 and the epithelin/granulin protein [8].
  • Reactivity of amino groups, phenoxy groups of tyrosine residues and some other charged groups of Tricoplusia ni granulosis virus granulin, which had rigid subunit structure abundant in beta-configuration, was investigated [9].

Biological context of Diamazo

  • Binding of granulin to P-TEFb inhibited the phosphorylation of a CTD peptide [2].
  • Granulins DE and E repress transcription from the HIV-1 LTR and gene expression from the viral genome, raising the possibility of developing granulin-based inhibitors of viral infection [10].
  • In this study, goldfish granulin was one of the most commonly identified transcripts in the differential cross-screening of macrophage cDNA libraries and was preferentially expressed in proliferating macrophages [11].
  • These results indicate that goldfish granulin is a growth factor that positively modulates cell proliferation at distinct junctures of macrophage differentiation [11].
  • The existence of a large molecular mass precursor for granulin or epithelin has been predicted based upon recently cloned cDNAs encoding these biomolecules within a 63.5-kDa protein with putative glycosylation sites [12].

Anatomical context of Diamazo

  • Recombinant goldfish granulin induced a dose-dependent proliferative response of goldfish macrophages that was inversely related to the myeloid differentiation stage of the cells studied [11].
  • The present results indicate that PCDGF is a potential precursor for epithelin and/or granulin, that this 88-kDa protein is secreted and glycosylated, and that it can function as a mitogen for 3T3 cells as well as an autocrine growth factor for PC cells [12].
  • Since one hallmark of embryo development is the formation of an epithelium, the trophectoderm, we tested the hypothesis that one such embryo-derived growth factor is acrogranin (epithelin/granulin precursor), a factor that possesses growth-regulatory activities principally toward epithelial cells [13].
  • Taken together, these results indicate that the intermediate of RD21 was accumulated in the vacuoles as an aggregate, and then slowly matured to make a soluble protease by removing the granulin domain during leaf senescence [14].
  • Thirty-six of these residues (78.3%) were identical to those of a recently cloned human neutrophil peptide of unknown function and belonging to the granulin family [15].

Associations of Diamazo with other chemical compounds

  • Granulin bound to the histidine-rich domain of cyclin T1, which was recently found to bind to the CTD, but not to cyclin T2 [2].
  • Unlike other members of the papain family, RD21 has a C-terminal extension sequence composed of two domains, a 2-kD proline-rich domain and a 10-kD domain homologous to animal epithelin/granulin family proteins [14].
  • Induction of granulin precursor gene expression by estrogen treatment in neonatal rat hypothalamus [16].
  • Our previous research has demonstrated that androgen treatment during the perinatal period increases granulin (grn) precursor mRNA levels in the neonatal rat hypothalamus [16].
  • Furthermore, the primary structures of guinea pig and mouse acrogranins, deduced from the cDNA sequences, reveal that this glycoprotein is a cysteine-rich molecule with a motif that is tandemly repeated seven times, very similar to that of the human epithelin/granulin precursor [17].

Gene context of Diamazo


Analytical, diagnostic and therapeutic context of Diamazo

  • Northern blot and real-time PCR analyses indicated that goldfish granulin was expressed only in the hematopoietic tissues of the goldfish, specifically the kidney and spleen, and in activated peripheral blood mononuclear cells [11].
  • The growth factor, purified to homogeneity by SDS-polyacrylamide gel electrophoresis, was identified as the granulin/epithelin precursor by an accurate determination of the masses of endoproteinase Lys-C peptides using matrix-assisted laser desorption ionization mass spectrometry, followed by a data base search [22].
  • The granulin gene region of Cryptophlebia leucotreta granulosis virus: sequence analysis and phylogenetic considerations [23].
  • T. ni larval bioassays showed that a factor, present in the TnGV granulin or AcMNPV polyhedrin, enhanced the infectivity of AcMNPV [24].
  • Comparison of mRNA levels by semi-quantitative RT-PCR revealed a relative overexpression of three genes in cancer tissues, including growth factor granulin and Tbdn-1--an orthologue of the mouse acetyltransferase gene which is associated with blood vessel development [25].


  1. Inhibition of PC cell-derived growth factor (PCDGF, epithelin/granulin precursor) expression by antisense PCDGF cDNA transfection inhibits tumorigenicity of the human breast carcinoma cell line MDA-MB-468. Lu, R., Serrero, G. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  2. The growth factor granulin interacts with cyclin T1 and modulates P-TEFb-dependent transcription. Hoque, M., Young, T.M., Lee, C.G., Serrero, G., Mathews, M.B., Pe'ery, T. Mol. Cell. Biol. (2003) [Pubmed]
  3. Identification of a human glioma-associated growth factor gene, granulin, using differential immuno-absorption. Liau, L.M., Lallone, R.L., Seitz, R.S., Buznikov, A., Gregg, J.P., Kornblum, H.I., Nelson, S.F., Bronstein, J.M. Cancer Res. (2000) [Pubmed]
  4. Evidence for zinc binding by two structural proteins of Plodia interpunctella granulosis virus. Funk, C.J., Consigli, R.A. J. Virol. (1992) [Pubmed]
  5. Effects of substituting granulin or a granulin-polyhedrin chimera for polyhedrin on virion occlusion and polyhedral morphology in Autographa californica multinucleocapsid nuclear polyhedrosis virus. Eason, J.E., Hice, R.H., Johnson, J.J., Federici, B.A. J. Virol. (1998) [Pubmed]
  6. The hairpin stack fold, a novel protein architecture for a new family of protein growth factors. Hrabal, R., Chen, Z., James, S., Bennett, H.P., Ni, F. Nat. Struct. Biol. (1996) [Pubmed]
  7. Isolation and sequence of the granulin precursor cDNA from human bone marrow reveals tandem cysteine-rich granulin domains. Bhandari, V., Palfree, R.G., Bateman, A. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  8. The Tat protein of the caprine arthritis encephalitis virus interacts with the Notch2 EGF-like repeats and the epithelin/granulin precursor. Shoham, N., Cohen, L., Gazit, A., Yaniv, A. Intervirology (2003) [Pubmed]
  9. Masking of some charged groups in a protein with beta-structure. Egawa, K. Jpn. J. Exp. Med. (1975) [Pubmed]
  10. Granulin and granulin repeats interact with the Tat.P-TEFb complex and inhibit Tat transactivation. Hoque, M., Tian, B., Mathews, M.B., Pe'ery, T. J. Biol. Chem. (2005) [Pubmed]
  11. A novel hematopoietic granulin induces proliferation of goldfish (Carassius auratus L.) macrophages. Hanington, P.C., Barreda, D.R., Belosevic, M. J. Biol. Chem. (2006) [Pubmed]
  12. Purification of an autocrine growth factor homologous with mouse epithelin precursor from a highly tumorigenic cell line. Zhou, J., Gao, G., Crabb, J.W., Serrero, G. J. Biol. Chem. (1993) [Pubmed]
  13. Modulation of mouse preimplantation embryo development by acrogranin (epithelin/granulin precursor). Díaz-Cueto, L., Stein, P., Jacobs, A., Schultz, R.M., Gerton, G.L. Dev. Biol. (2000) [Pubmed]
  14. A slow maturation of a cysteine protease with a granulin domain in the vacuoles of senescing Arabidopsis leaves. Yamada, K., Matsushima, R., Nishimura, M., Hara-Nishimura, I. Plant Physiol. (2001) [Pubmed]
  15. Identification of eNAP-1, an antimicrobial peptide from equine neutrophils. Couto, M.A., Harwig, S.S., Cullor, J.S., Hughes, J.P., Lehrer, R.I. Infect. Immun. (1992) [Pubmed]
  16. Induction of granulin precursor gene expression by estrogen treatment in neonatal rat hypothalamus. Suzuki, M., Yonezawa, T., Fujioka, H., Matuamuro, M., Nishihara, M. Neurosci. Lett. (2001) [Pubmed]
  17. Acrogranin, an acrosomal cysteine-rich glycoprotein, is the precursor of the growth-modulating peptides, granulins, and epithelins, and is expressed in somatic as well as male germ cells. Baba, T., Hoff, H.B., Nemoto, H., Lee, H., Orth, J., Arai, Y., Gerton, G.L. Mol. Reprod. Dev. (1993) [Pubmed]
  18. The human platelet alphaIIb gene is not closely linked to its integrin partner beta3. Thornton, M.A., Poncz, M., Korostishevsky, M., Yakobson, E., Usher, S., Seligsohn, U., Peretz, H. Blood (1999) [Pubmed]
  19. Phylogenetic analysis of conserved genes within the ecdysteroid UDP-glucosyltransferase gene region of the slow-killing Adoxophyes orana granulovirus. Wormleaton, S.L., Winstanley, D. J. Gen. Virol. (2001) [Pubmed]
  20. Somatostatin-, vasoactive intestinal peptide-, and granulin-like peptides isolated from intestinal extracts of goldfish, Carassius auratus. Uesaka, T., Yano, K., Yamasaki, M., Ando, M. Gen. Comp. Endocrinol. (1995) [Pubmed]
  21. Inhibition of tumorigenicity of the teratoma PC cell line by transfection with antisense cDNA for PC cell-derived growth factor (PCDGF, epithelin/granulin precursor). Zhang, H., Serrero, G. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  22. The granulin/epithelin precursor abrogates the requirement for the insulin-like growth factor 1 receptor for growth in vitro. Xu, S.Q., Tang, D., Chamberlain, S., Pronk, G., Masiarz, F.R., Kaur, S., Prisco, M., Zanocco-Marani, T., Baserga, R. J. Biol. Chem. (1998) [Pubmed]
  23. The granulin gene region of Cryptophlebia leucotreta granulosis virus: sequence analysis and phylogenetic considerations. Jehle, J.A., Backhaus, H. J. Gen. Virol. (1994) [Pubmed]
  24. Alteration of a lepidopteran peritrophic membrane by baculoviruses and enhancement of viral infectivity. Derksen, A.C., Granados, R.R. Virology (1988) [Pubmed]
  25. Serological identification and expression analysis of gastric cancer-associated genes. Linē, A., Stengrēvics, A., Slucka, Z., Li, G., Jankevics, E., Rees, R.C. Br. J. Cancer (2002) [Pubmed]
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