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Gene Review

CFL1  -  cofilin 1 (non-muscle)

Homo sapiens

Synonyms: 18 kDa phosphoprotein, CFL, Cofilin, non-muscle isoform, Cofilin-1, HEL-S-15, ...
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Disease relevance of CFL1


Psychiatry related information on CFL1

  • 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].
  • Two standardized neuropsychological word-generation tasks (controlled word-association tests: CFL and Animals) were then administered (4 minutes total) followed again by the two baseline procedures [7].
  • Participants completed neuropsychological testing with the Dementia Rating Scale (DRS), Logical Memory, and CFL Word Fluency. There were no significant demographic group differences, although seniors with epilepsy had higher self-reported depression [8].

High impact information on CFL1


Chemical compound and disease context of CFL1


Biological context of CFL1


Anatomical context of CFL1


Associations of CFL1 with chemical compounds

  • LIMK-1 phosphorylation and cofilin dephosphorylation and rephosphorylation during aggregation were independent of integrin alpha(IIb)beta(3) engagement [18].
  • Ouabain-sensitive (86)Rb(+) uptake showed that Na,K-ATPase activity was increased by the overexpression of cofilin and lysophosphatidic acid treatment, but not by the overexpression of mutant cofilin S3A and Y-27632 treatment [21].
  • Pretreatment with the glycolytic inhibitor iodoacetic acid caused a remarkable reduction of Na,K-ATPase activity, whereas pretreatment with the oxidative inhibitor carbonyl cyanide m-chlorophenylhydrazone caused no detectable changes, suggesting that the phosphorylated cofilin is involved in feeding glycolytic fuel for Na,K-ATPase activity [21].
  • Importantly, knockdown of SSH1L expression by RNA interference abolished A23187- or calcineurin-induced cofilin dephosphorylation [23].
  • Phosphoinositide 3-kinase-mediated activation of cofilin phosphatase Slingshot and its role for insulin-induced membrane protrusion [24].

Physical interactions of CFL1

  • We demonstrated that dual regulation of cyclic AMP and Ca2+ determines cofilin (an actin-binding protein) phosphorylation states and LIM kinase 1 (a cofilin kinase) expression level during neuritogenesis [25].
  • These results are consistent with a model in which pH-dependent motion of subdomain 1 relative to subdomain 2 (through region 75-105) of actin reveals a second cofilin binding site on actin (centered around region 112-125) that allows ADF/cofilin association with the actin filament [26].

Enzymatic interactions of CFL1

  • Surprisingly, during shape change cofilin phosphorylation was unaltered, and during aggregation/secretion cofilin was first rapidly dephosphorylated by an okadaic acid-insensitive phosphatase and then slowly rephosphorylated by LIMK-1 [18].
  • These results suggest that SSH1 plays a critical role in cytokinesis by dephosphorylating and reactivating cofilin in later stages of mitosis [27].
  • Like LIM-kinases, TESK1 phosphorylated cofilin specifically at Ser-3, both in vitro and in vivo [22].
  • Further, we examined the localization of the phosphorylated form of cofilin using phospho-specific antibody raised against phosphorylated cofilin [28].
  • CIN directly dephosphorylates cofilin with high specificity and colocalizes with cofilin in motile and dividing cells [29].

Regulatory relationships of CFL1


Other interactions of CFL1


Analytical, diagnostic and therapeutic context of CFL1

  • Expression of non-phosphorylatable mutant cofilin proteins in NIH3T3 cells and determination of their subcellular localization by confocal laser scanning microscopy reveal that non-phosphorylated cofilin accumulates within nuclei [36].
  • Filaments of cofilin-decorated TMR-actin and unlabeled actin are indistinguishable, as revealed by electron microscopy and three-dimensional reconstruction [37].
  • The de-phosphorylation of cofilin-1 was confirmed using western blotting of UV-exposed skin equivalents and ex vivo skin protein extracts [38].
  • These two proteins were identified as the phosphorylated and non-phosphorylated forms of the pH-sensitive actin-depolymerizing protein, cofilin, by sequencing of peptide fragments and immunoblotting with a monoclonal antibody specific for cofilin [39].
  • To determine whether the DNA repair capacity was altered in cofilin over-expressing cells, comet assays were performed on irradiated cells [5].


  1. Association between CFL1 gene polymorphisms and spina bifida risk in a California population. Zhu, H., Enaw, J.O., Ma, C., Shaw, G.M., Lammer, E.J., Finnell, R.H. BMC Med. Genet. (2007) [Pubmed]
  2. Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase. Maekawa, M., Ishizaki, T., Boku, S., Watanabe, N., Fujita, A., Iwamatsu, A., Obinata, T., Ohashi, K., Mizuno, K., Narumiya, S. Science (1999) [Pubmed]
  3. LIM kinase 1 is essential for the invasive growth of prostate epithelial cells: implications in prostate cancer. Davila, M., Frost, A.R., Grizzle, W.E., Chakrabarti, R. J. Biol. Chem. (2003) [Pubmed]
  4. Efficient Salmonella entry requires activity cycles of host ADF and cofilin. Dai, S., Sarmiere, P.D., Wiggan, O., Bamburg, J.R., Zhou, D. Cell. Microbiol. (2004) [Pubmed]
  5. Enhancement of radiosensitivity in H1299 cancer cells by actin-associated protein cofilin. Lee, Y.J., Sheu, T.J., Keng, P.C. Biochem. Biophys. Res. Commun. (2005) [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. Near-infrared spectroscopy to define cognitive frontal lobe functions. Jayakar, A., Dunoyer, C., Rey, G., Yaylali, I., Jayakar, P. Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society. (2005) [Pubmed]
  8. Older adults with epilepsy demonstrate cognitive impairments compared with patients with amnestic mild cognitive impairment. Griffith, H.R., Martin, R.C., Bambara, J.K., Marson, D.C., Faught, E. Epilepsy & behavior : E&B. (2006) [Pubmed]
  9. Control of actin reorganization by Slingshot, a family of phosphatases that dephosphorylate ADF/cofilin. Niwa, R., Nagata-Ohashi, K., Takeichi, M., Mizuno, K., Uemura, T. Cell (2002) [Pubmed]
  10. Tertiary structure of destrin and structural similarity between two actin-regulating protein families. Hatanaka, H., Ogura, K., Moriyama, K., Ichikawa, S., Yahara, I., Inagaki, F. Cell (1996) [Pubmed]
  11. Cofilin phosphorylation by LIM-kinase 1 and its role in Rac-mediated actin reorganization. Yang, N., Higuchi, O., Ohashi, K., Nagata, K., Wada, A., Kangawa, K., Nishida, E., Mizuno, K. Nature (1998) [Pubmed]
  12. Pathophysiology and functional significance of apical membrane disruption during ischemia. Ashworth, S.L., Molitoris, B.A. Curr. Opin. Nephrol. Hypertens. (1999) [Pubmed]
  13. Prohibitin and Cofilin Are Intracellular Effectors of Transforming Growth Factor {beta} Signaling in Human Prostate Cancer Cells. Zhu, B., Fukada, K., Zhu, H., Kyprianou, N. Cancer Res. (2006) [Pubmed]
  14. Inhibition of constitutive serine phosphatase activity in T lymphoma cells results in phosphorylation of pp19/cofilin and induces apoptosis. Samstag, Y., Dreizler, E.M., Ambach, A., Sczakiel, G., Meuer, S.C. J. Immunol. (1996) [Pubmed]
  15. Integrin alpha(IIb)beta3 signals lead cofilin to accelerate platelet actin dynamics. Falet, H., Chang, G., Brohard-Bohn, B., Rendu, F., Hartwig, J.H. Am. J. Physiol., Cell Physiol. (2005) [Pubmed]
  16. Clinical chemotherapeutic evaluation of fosfomycin plus amoxicillin (co-fosfolactamine): a prospective double-blind clinical trial. Novelli, A., Rizzo, M., Buzzoni, P., Coronnello, M., Alunno Pergentini, S., Giganti, E., Periti, P. Chemioterapia : international journal of the Mediterranean Society of Chemotherapy. (1984) [Pubmed]
  17. Spatial and temporal regulation of cofilin activity by LIM kinase and Slingshot is critical for directional cell migration. Nishita, M., Tomizawa, C., Yamamoto, M., Horita, Y., Ohashi, K., Mizuno, K. J. Cell Biol. (2005) [Pubmed]
  18. Regulation of LIM-kinase 1 and cofilin in thrombin-stimulated platelets. Pandey, D., Goyal, P., Bamburg, J.R., Siess, W. Blood (2006) [Pubmed]
  19. Cofilin interacts with ClC-5 and regulates albumin uptake in proximal tubule cell lines. Hryciw, D.H., Wang, Y., Devuyst, O., Pollock, C.A., Poronnik, P., Guggino, W.B. J. Biol. Chem. (2003) [Pubmed]
  20. Cofilin phosphorylation and actin reorganization activities of testicular protein kinase 2 and its predominant expression in testicular Sertoli cells. Toshima, J., Toshima, J.Y., Takeuchi, K., Mori, R., Mizuno, K. J. Biol. Chem. (2001) [Pubmed]
  21. Interaction of cofilin with triose-phosphate isomerase contributes glycolytic fuel for Na,K-ATPase via Rho-mediated signaling pathway. Jung, J., Yoon, T., Choi, E.C., Lee, K. J. Biol. Chem. (2002) [Pubmed]
  22. Cofilin phosphorylation by protein kinase testicular protein kinase 1 and its role in integrin-mediated actin reorganization and focal adhesion formation. Toshima, J., Toshima, J.Y., Amano, T., Yang, N., Narumiya, S., Mizuno, K. Mol. Biol. Cell (2001) [Pubmed]
  23. Calcium signal-induced cofilin dephosphorylation is mediated by Slingshot via calcineurin. Wang, Y., Shibasaki, F., Mizuno, K. J. Biol. Chem. (2005) [Pubmed]
  24. Phosphoinositide 3-kinase-mediated activation of cofilin phosphatase Slingshot and its role for insulin-induced membrane protrusion. Nishita, M., Wang, Y., Tomizawa, C., Suzuki, A., Niwa, R., Uemura, T., Mizuno, K. J. Biol. Chem. (2004) [Pubmed]
  25. Signal transduction cascades underlying de novo protein synthesis required for neuronal morphogenesis in differentiating neurons. Tojima, T., Ito, E. Prog. Neurobiol. (2004) [Pubmed]
  26. A structural basis for the pH-dependence of cofilin. F-actin interactions. Blondin, L., Sapountzi, V., Maciver, S.K., Lagarrigue, E., Benyamin, Y., Roustan, C. Eur. J. Biochem. (2002) [Pubmed]
  27. Cell cycle-associated changes in Slingshot phosphatase activity and roles in cytokinesis in animal cells. Kaji, N., Ohashi, K., Shuin, M., Niwa, R., Uemura, T., Mizuno, K. J. Biol. Chem. (2003) [Pubmed]
  28. Suppression of cofilin phosphorylation in insulin-stimulated ruffling membrane formation in KB cells. Arai, H., Atomi, Y. Cell Struct. Funct. (2003) [Pubmed]
  29. Chronophin, a novel HAD-type serine protein phosphatase, regulates cofilin-dependent actin dynamics. Gohla, A., Birkenfeld, J., Bokoch, G.M. Nat. Cell Biol. (2005) [Pubmed]
  30. Control of growth cone motility and morphology by LIM kinase and Slingshot via phosphorylation and dephosphorylation of cofilin. Endo, M., Ohashi, K., Sasaki, Y., Goshima, Y., Niwa, R., Uemura, T., Mizuno, K. J. Neurosci. (2003) [Pubmed]
  31. Par-3 mediates the inhibition of LIM kinase 2 to regulate cofilin phosphorylation and tight junction assembly. Chen, X., Macara, I.G. J. Cell Biol. (2006) [Pubmed]
  32. A role of LIM kinase 1/cofilin pathway in regulating endocytic trafficking of EGF receptor in human breast cancer cells. Nishimura, Y., Yoshioka, K., Bernard, O., Bereczky, B., Itoh, K. Histochem. Cell Biol. (2006) [Pubmed]
  33. A pathway of neuregulin-induced activation of cofilin-phosphatase Slingshot and cofilin in lamellipodia. Nagata-Ohashi, K., Ohta, Y., Goto, K., Chiba, S., Mori, R., Nishita, M., Ohashi, K., Kousaka, K., Iwamatsu, A., Niwa, R., Uemura, T., Mizuno, K. J. Cell Biol. (2004) [Pubmed]
  34. Cytoskeletal changes regulated by the PAK4 serine/threonine kinase are mediated by LIM kinase 1 and cofilin. Dan, C., Kelly, A., Bernard, O., Minden, A. J. Biol. Chem. (2001) [Pubmed]
  35. Solution structure of human cofilin: actin binding, pH sensitivity, and relationship to actin-depolymerizing factor. Pope, B.J., Zierler-Gould, K.M., Kühne, R., Weeds, A.G., Ball, L.J. J. Biol. Chem. (2004) [Pubmed]
  36. Dephosphorylation of serine 3 regulates nuclear translocation of cofilin. Nebl, G., Meuer, S.C., Samstag, Y. J. Biol. Chem. (1996) [Pubmed]
  37. Cofilin cross-bridges adjacent actin protomers and replaces part of the longitudinal F-actin interface. Kudryashov, D.S., Galkin, V.E., Orlova, A., Phan, M., Egelman, E.H., Reisler, E. J. Mol. Biol. (2006) [Pubmed]
  38. Proteomic profiling identifies an UV-induced activation of cofilin-1 and destrin in human epidermis. Hensbergen, P., Alewijnse, A., Kempenaar, J., van der Schors, R.C., van der Schors, R., Balog, C.A., Deelder, A., Beumer, G., Ponec, M., Tensen, C.P. J. Invest. Dermatol. (2005) [Pubmed]
  39. Dephosphorylation of cofilin in stimulated platelets: roles for a GTP-binding protein and Ca2+. Davidson, M.M., Haslam, R.J. Biochem. J. (1994) [Pubmed]
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