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Gene Review

GSN  -  gelsolin

Homo sapiens

Synonyms: ADF, AGEL, Actin-depolymerizing factor, Brevin, DKFZp313L0718, ...
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Disease relevance of GSN


Psychiatry related information on GSN

  • However, we could detect no difference in the levels of expression of either ADF or cofilin in the hippocampal tissue from normal individuals and Alzheimer's disease patients [6].

High impact information on GSN

  • Adult T cell leukemia-derived factor (ADF), which we originally defined as an IL-2 receptor alpha-chain/Tac inducer produced by human T cell lymphotrophic virus-I (HTLV-I)-transformed T cells, has been identified as human TRX [7].
  • Extracellularly, TRX/ADF shows a cytoprotective activity against oxidative stress-induced apoptosis and a growth-promoting effect as an autocrine growth factor [7].
  • For example, TRX/ADF translocates from the cytosol into the nucleus by a variety of cellular stresses, to regulate the expression of various genes through the redox factor-1 (Ref-1)/APEX [7].
  • Intracellularly, TRX/ADF is involved in the regulation of protein-protein or protein-nucleic acid interactions through the reduction/oxidation of protein cysteine residues [7].
  • Using GSN polymorphisms, different haplotypes were found in the Danish and Czech families [1].

Chemical compound and disease context of GSN


Biological context of GSN

  • Linkage of a gene causing classic dystonia in a large non-Jewish kindred (DYT1) and in a group of Ashkenazi Jewish families, to the gelsolin (GSN) and arginino-succinate synthetase (ASS) loci on chromosome 9q32-34, respectively, was recently determined [13].
  • Age-dependent transcription factor (ADF) interacts with prostate-specific antigen (PSA) gene enhancer [14].
  • This suggests that ADF may play a role in the regulation of PSA gene expression [14].
  • Our data indicate that treatment of hippocampal neurons with fAbeta increases the level of Ser3-phosphorylated ADF/cofilin and Thr508-phosphorylated LIMK1 (P-LIMK1), accompanied by a dramatic remodeling of actin filaments, neuritic dystrophy, and neuronal cell death [15].
  • Thus, ADF and cofilin are coordinately regulated by posttranslational modification, but their expression is differentially regulated [16].

Anatomical context of GSN

  • These results suggest that LIMK2 functions downstream of the Rho-ROCK signalling pathway and plays a role in reorganization of actin filaments and membrane structures, by phosphorylating cofilin/ADF proteins [17].
  • The specific transcripts for beta-actin and actin-depolymerizing factor (ADF) were also present and non-uniformly distributed in axons, with an approximately hundredfold higher concentration in growth cones, branch points and axonal varicosities than in the axon shaft [18].
  • Myoblasts, transfected with a human gene encoding a beta-actin point mutation, down-regulate expression of actin depolymerizing factor (ADF) and its mRNA [16].
  • MATERIALS AND METHODS: The 2 human bladder cancer cell lines KU-7 and UMUC-2 were transduced with Ad-GSN in vitro [19].
  • In vivo KU-7 cells were introduced into the bladder of nude mice (day 0), followed by 3 injections into the urethra (days 2 to 4) with Ad-GSN or Ad-betagal (1 x 10 pfu) [19].

Associations of GSN with chemical compounds

  • We conclude that substitution of the uncharged Asn or Tyr for the acidic Asp at residue 187 creates a conformation that may be preferentially amyloidogenic for GSN [1].
  • Together, these data suggest that the weak androgenic effect of HF may be amplified by increasing the amount of GSN after androgen ablation treatment [2].
  • Cofilin/ADF, beryllium fluoride complex (BeFx), and phalloidin have opposing effects on actin filament structure and dynamics [20].
  • 1. Impulse activity in an identified serotonin-containing neuron (GSN) produces a slow excitatory synaptic response in another identified neuron, the A neuron [21].
  • 8. Cyproheptadine (reversibly), methergoline, mianserin and propranolol (all irreversibly) antagonised the response in the GSN [21].
  • When COS-1 cells transiently transfected with gelsolin cDNA were treated with etoposide or staurosporine, apoptosis-inducing agents, N-myristoylated tGelsolin was generated, as demonstrated by in vivo metabolic labeling [22].

Physical interactions of GSN

  • GSN interacts with AR DNA-binding domain and ligand-binding domain via its COOH-terminal domain [2].

Regulatory relationships of GSN

  • Functional analyses additionally demonstrate that GSN enhances AR activity in the presence of either androgen or HF [2].

Other interactions of GSN

  • The amino terminal sequence of this 12 kDa amyloid protein (ATEVPVSWESFNNGD) showed homology with gelsolin (or actin depolymerizing factor), a 93 kDa plasma protein [23].
  • TPSS is now or soon will be available in standard codes such as GAUSSIAN, TURBOMOLE, NWCHEM, ADF, WIEN, VASP, etc [24].
  • Brevin, like gelsolin from macrophages and villin from intestinal brush border, also appears capable of severing preformed actin filaments and disrupting filament networks as measured with a low-shear falling ball viscometer [25].

Analytical, diagnostic and therapeutic context of GSN

  • The expression of GSN is enhanced in LNCaP cells, LNCaP xenografts, and human prostate tumors after androgen depletion [2].
  • Immunoprecipitation using specific antibodies indicates that beta-actin, ADF and neurofilament protein (NF) are translated in axons independently of cell bodies [18].
  • We examined the activation of cofilin, an actin-depolymerizing factor, in lupeol-treated B16 2F2 cells by western blotting [26].
  • Here, we demonstrate by competitive electrophoretic mobility shift assay that ADF binds to a 19 bp sequence in PSA gene (-4372 to -4390) located within this enhancer region [14].
  • In this work, we genotyped 3 SNPs around the GSN locus in 493 sets of the Han Chinese trio sample using allele-specific PCR [27].


  1. Gelsolin-derived familial amyloidosis caused by asparagine or tyrosine substitution for aspartic acid at residue 187. de la Chapelle, A., Tolvanen, R., Boysen, G., Santavy, J., Bleeker-Wagemakers, L., Maury, C.P., Kere, J. Nat. Genet. (1992) [Pubmed]
  2. Modulation of androgen receptor transactivation by gelsolin: a newly identified androgen receptor coregulator. Nishimura, K., Ting, H.J., Harada, Y., Tokizane, T., Nonomura, N., Kang, H.Y., Chang, H.C., Yeh, S., Miyamoto, H., Shin, M., Aozasa, K., Okuyama, A., Chang, C. Cancer Res. (2003) [Pubmed]
  3. Gelsolin variant (Asn-187) in familial amyloidosis, Finnish type. Ghiso, J., Haltia, M., Prelli, F., Novello, J., Frangione, B. Biochem. J. (1990) [Pubmed]
  4. ADF, a growth-promoting factor derived from adult T cell leukemia and homologous to thioredoxin: involvement in lymphocyte immortalization by HTLV-I and EBV. Yodoi, J., Tursz, T. Adv. Cancer Res. (1991) [Pubmed]
  5. Increased expression of human thioredoxin/adult T cell leukemia-derived factor in Sjögren's syndrome. Saito, I., Shimuta, M., Terauchi, K., Tsubota, K., Yodoi, J., Miyasaka, N. Arthritis Rheum. (1996) [Pubmed]
  6. Two actin binding proteins, actin depolymerizing factor and cofilin, are associated with Hirano bodies. Maciver, S.K., Harrington, C.R. Neuroreport (1995) [Pubmed]
  7. Redox regulation of cellular activation. Nakamura, H., Nakamura, K., Yodoi, J. Annu. Rev. Immunol. (1997) [Pubmed]
  8. Beta-secretase-cleaved amyloid precursor protein accumulates at actin inclusions induced in neurons by stress or amyloid beta: a feedforward mechanism for Alzheimer's disease. Maloney, M.T., Minamide, L.S., Kinley, A.W., Boyle, J.A., Bamburg, J.R. J. Neurosci. (2005) [Pubmed]
  9. Scavenging system efficiency is crucial for cell resistance to ROS-mediated methylglyoxal injury. Amicarelli, F., Colafarina, S., Cattani, F., Cimini, A., Di Ilio, C., Ceru, M.P., Miranda, M. Free Radic. Biol. Med. (2003) [Pubmed]
  10. Human glioblastoma ADF cells express tyrosinase, L-tyrosine hydroxylase and melanosomes and are sensitive to L-tyrosine and phenylthiourea. Bonfigli, A., Zarivi, O., Colafarina, S., Cimini, A.M., Ragnelli, A.M., Aimola, P., Natali, P.G., Cerù, M.P., Amicarelli, F., Miranda, M. J. Cell. Physiol. (2006) [Pubmed]
  11. PPARgamma-dependent effects of conjugated linoleic acid on the human glioblastoma cell line (ADF). Cimini, A., Cristiano, L., Colafarina, S., Benedetti, E., Di Loreto, S., Festuccia, C., Amicarelli, F., Canuto, R.A., Cerù, M.P. Int. J. Cancer (2005) [Pubmed]
  12. Analysis of localization of adult T-cell leukemia-derived factor in the transient ischemic rat retina after treatment with OP-1206 alpha-CD, a prostaglandin E1 analogue. Yamamoto, M., Ohira, A., Honda, O., Sato, N., Furuke, K., Yodoi, J., Honda, Y. J. Histochem. Cytochem. (1997) [Pubmed]
  13. Identification of a highly polymorphic microsatellite VNTR within the argininosuccinate synthetase locus: exclusion of the dystonia gene on 9q32-34 as the cause of dopa-responsive dystonia in a large kindred. Kwiatkowski, D.J., Nygaard, T.G., Schuback, D.E., Perman, S., Trugman, J.M., Bressman, S.B., Burke, R.E., Brin, M.F., Ozelius, L., Breakefield, X.O. Am. J. Hum. Genet. (1991) [Pubmed]
  14. Age-dependent transcription factor (ADF) interacts with prostate-specific antigen (PSA) gene enhancer. Zaidi, G., Supakar, P.C. Mol. Biol. Rep. (2002) [Pubmed]
  15. Phosphorylation of actin-depolymerizing factor/cofilin by LIM-kinase mediates amyloid beta-induced degeneration: a potential mechanism of neuronal dystrophy in Alzheimer's disease. Heredia, L., Helguera, P., de Olmos, S., Kedikian, G., Solá Vigo, F., LaFerla, F., Staufenbiel, M., de Olmos, J., Busciglio, J., Cáceres, A., Lorenzo, A. J. Neurosci. (2006) [Pubmed]
  16. Differential regulation of actin depolymerizing factor and cofilin in response to alterations in the actin monomer pool. Minamide, L.S., Painter, W.B., Schevzov, G., Gunning, P., Bamburg, J.R. J. Biol. Chem. (1997) [Pubmed]
  17. LIM-kinase 2 induces formation of stress fibres, focal adhesions and membrane blebs, dependent on its activation by Rho-associated kinase-catalysed phosphorylation at threonine-505. Amano, T., Tanabe, K., Eto, T., Narumiya, S., Mizuno, K. Biochem. J. (2001) [Pubmed]
  18. Organization and translation of mRNA in sympathetic axons. Lee, S.K., Hollenbeck, P.J. J. Cell. Sci. (2003) [Pubmed]
  19. Adenovirus mediated gelsolin gene therapy for orthotopic human bladder cancer in nude mice. Sazawa, A., Watanabe, T., Tanaka, M., Haga, K., Fujita, H., Harabayashi, T., Shinohara, N., Koyanagi, T., Kuzumaki, N. J. Urol. (2002) [Pubmed]
  20. Antagonistic effects of cofilin, beryllium fluoride complex, and phalloidin on subdomain 2 and nucleotide-binding cleft in f-actin. Muhlrad, A., Ringel, I., Pavlov, D., Peyser, Y.M., Reisler, E. Biophys. J. (2006) [Pubmed]
  21. Voltage-dependent actions of endogenous and exogenous serotonin on identified neurones. Cottrell, G.A. Comp. Biochem. Physiol. C, Comp. Pharmacol. (1982) [Pubmed]
  22. Posttranslational N-myristoylation is required for the anti-apoptotic activity of human tGelsolin, the C-terminal caspase cleavage product of human gelsolin. Sakurai, N., Utsumi, T. J. Biol. Chem. (2006) [Pubmed]
  23. Amyloid protein in familial amyloidosis (Finnish type) is homologous to gelsolin, an actin-binding protein. Haltia, M., Prelli, F., Ghiso, J., Kiuru, S., Somer, H., Palo, J., Frangione, B. Biochem. Biophys. Res. Commun. (1990) [Pubmed]
  24. Prescription for the design and selection of density functional approximations: more constraint satisfaction with fewer fits. Perdew, J.P., Ruzsinszky, A., Tao, J., Staroverov, V.N., Scuseria, G.E., Csonka, G.I. The Journal of chemical physics. (2005) [Pubmed]
  25. Brevin, a serum protein that acts on the barbed end of actin filaments. Wilkins, J.A., Schwartz, J.H., Harris, D.A. Cell Biol. Int. Rep. (1983) [Pubmed]
  26. Remodeling of actin cytoskeleton in lupeol-induced B16 2F2 cell differentiation. Hata, K., Hori, K., Murata, J., Takahashi, S. J. Biochem. (2005) [Pubmed]
  27. Transmission disequilibrium analysis of the GSN gene in a cohort of family trios with schizophrenia. Xi, Z.R., Qin, W., Yang, Y.F., He, G., Gao, S.H., Ren, M.S., Peng, Y.W., Zhang, Z., He, L. Neurosci. Lett. (2004) [Pubmed]
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