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Gene Review

Anxa1  -  annexin A1

Mus musculus

Synonyms: Annexin A1, Annexin I, Annexin-1, Anx-1, Anx-A1, ...
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Disease relevance of Anxa1


High impact information on Anxa1

  • Blocked negative selection of developing T cells in mice expressing the baculovirus p35 caspase inhibitor [6].
  • We have purified two phospholipase A2 inhibitory proteins (37 and 33 kDa) from peritoneal fluid of dexamethasone-treated rats [7].
  • Dexamethasone induces the synthesis of a phospholipase A2-inhibitory protein (PLIP) of molecular weight approximately equal to 55,000 from calf thymus and PLIPs of molecular weights 55,000, 40,000, 28,000, and 15,000 from A/J mouse thymus and from 12-day embryonic B10 [8].
  • Sufficient quantities of calf thymus PLIP and of the 15,000 molecular weight mouse thymus and palate PLIPs were prepared and tested as inhibitors of programmed cell death in the medial-edge epithelium of single mouse embryonic palatal shelves in culture [8].
  • This teratogenic action of both PLIP and glucocorticoids is reversed by arachidonic acid, the precursor of prostaglandins and thromboxanes, suggesting that PLIP mediates the effects of glucocorticoids by inhibiting phospholipase A2 [8].

Chemical compound and disease context of Anxa1


Biological context of Anxa1

  • Mouse brain cDNA library was introduced into a yeast strain in which Cdk5, p35 and mouse cDNA were over-expressed under the control of the GAL promoter, and cDNA plasmids were isolated from the transformants that recovered growth on galactose medium [1].
  • CONCLUSION: Anx-1 exerts endogenous antiinflammatory effects on AIA via the regulation of cytokine gene expression, and also mediates the antiinflammatory actions of dexamethasone in AIA [2].
  • Taken together, these observations suggest strongly that Anx-A1 functions as an inhibitor of signal-transduction pathways that lead to cell proliferation and may help to explain how glucocorticoids regulate these processes [10].
  • The Ca(2+)- and phospholipid-binding protein Anx-A1 (annexin 1; lipocortin 1) has been described both as an inhibitor of phospholipase A(2) (PLA(2)) activity and as a mediator of glucocorticoid-regulated cell growth and eicosanoid generation [10].
  • The phenotype of the AnxA1 null PMN was investigated in two in vitro assays of cell activation (CD11b membrane expression and chemotaxis): the data obtained indicated a higher degree of cellular responses irrespective of the stimulus used [3].

Anatomical context of Anxa1

  • Attenuation of glucocorticoid functions in an Anx-A1-/- cell line [10].
  • Here we show that, when compared with Anx-A1(+/+) cells, lung fibroblast cell lines derived from the Anx-A1(-/-) mouse exhibit an altered morphology characterized by a spindle-shaped appearance and an accumulation of intracellular organelles [10].
  • Intravital microscopy analysis of the cremaster microcirculation inflamed by zymosan (6 h time-point) indicated a greater extent of leukocyte emigration, but not rolling or adhesion, in AnxA1 null mice [3].
  • In conclusion, we have used a combination of inflammatory protocols and in vitro assays to address the specific counter-regulatory role of endogenous AnxA1, demonstrating its inhibitory control on PMN activation and the consequent impact on the inflamed microcirculation [3].
  • Several other anomalies were noted including abnormal leukocyte adhesion molecule expression, an increased spontaneous migratory behaviour of PMN in Anx-1(-/-) mice and a resistance in Anx-1(-/-) macrophages to glucocorticoid inhibition of superoxide generation [11].

Associations of Anxa1 with chemical compounds

  • These results indicate that exogenously administered Anxa1 can peripherally and centrally inhibit the nociceptive transmission associated with inflammatory processes through a mechanism that involves formyl peptide receptors [12].
  • However, lipoxin A4 (LXA4, 0.02-2 microM, a lipid mediator with high affinity for Fpr-rs1) mimicked the inhibitory effects of ANXA1 on ACTH release as also did fMLF in high (1-100 microM) but not lower (10-100 nM) concentrations [13].
  • In the present experiments, p35 mRNA accumulation was induced in splenic macrophages/dendritic cells by the interaction with paraformaldehyde-fixed Th1 cells in the presence of Ag, and the p35 mRNA accumulation was abrogated by the inclusion of anti-I-A in cultures to block TCR/MHC class II interaction [14].
  • In mutant mice with targeted deletion of p35, a neuronal specific activator of cdk5, roscovitine regulated calcium currents in a manner similar to that observed in wild-type mice [15].
  • We therefore conclude that this cAMP response element sequence plays a prominent role in the transactivation of the annexin A1 promoter by dibutyryl cAMP and that it is involved in the response to glucocorticoids [16].
  • Blockade of lipoxin A4 synthesis with a 5-lipoxygenase inhibitor or Abs against annexin-1 partially prevented IL-10 production and this was accompanied by partial reversion of inflammatory hyporesponsiveness in germfree mice [17].

Physical interactions of Anxa1

  • Here, we report that mice lacking the Anx-1 gene exhibit a complex phenotype that includes an altered expression of other annexins as well as of COX-2 and cPLA2 [18].

Regulatory relationships of Anxa1


Other interactions of Anxa1

  • Comparison of the genes coding for mouse and human p36 (annexin II) and mouse, rat and human p35 (annexin I) and pigeon cp35 (an annexin I-related protein) shows strong genomic structural conservation supporting the hypothesis that these genes had a common ancestor [20].
  • Unlike their wild-type counterparts, Anx-A1(-/-) cells also overexpress cyclo-oxygenase 2 (COX 2), cytosolic PLA(2) and secretory PLA(2) and in response to fetal calf serum, exhibit an exaggerated release of eicosanoids, which is insensitive to dexamethasone (10(-8)- 10(-6) M) inhibition [10].
  • Loss of the response to dexamethasone in Anx-A1(-/-) cells occurs against a background of no apparent change in glucocorticoid receptor expression or sensitivity to non-steroidal anti-inflammatory drugs [10].
  • In carrageenin- or zymosan-induced inflammation, Anx-1-/- mice exhibit an exaggerated response to the stimuli characterized by an increase in leukocyte emigration and IL-1beta generation and a partial or complete resistance to the antiinflammatory effects of glucocorticoids [18].
  • The production of the cytokines TNFalpha and IL-6 was increased in Anx-A1(-/-) macrophages following phagocytosis of all types of particle [21].

Analytical, diagnostic and therapeutic context of Anxa1


  1. Identifying novel substrates for mouse Cdk5 kinase using the yeast Saccharomyces cerevisiae. Horiuchi, Y., Asada, A., Hisanaga, S., Toh-E, A., Nishizawa, M. Genes Cells (2006) [Pubmed]
  2. Modulation of inflammation and response to dexamethasone by Annexin 1 in antigen-induced arthritis. Yang, Y.H., Morand, E.F., Getting, S.J., Paul-Clark, M., Liu, D.L., Yona, S., Hannon, R., Buckingham, J.C., Perretti, M., Flower, R.J. Arthritis Rheum. (2004) [Pubmed]
  3. Annexin 1-deficient neutrophils exhibit enhanced transmigration in vivo and increased responsiveness in vitro. Chatterjee, B.E., Yona, S., Rosignoli, G., Young, R.E., Nourshargh, S., Flower, R.J., Perretti, M. J. Leukoc. Biol. (2005) [Pubmed]
  4. Down-regulation of the anti-inflammatory protein annexin A1 in cystic fibrosis knock-out mice and patients. Bensalem, N., Ventura, A.P., Vallée, B., Lipecka, J., Tondelier, D., Davezac, N., Dos Santos, A., Perretti, M., Fajac, A., Sermet-Gaudelus, I., Renouil, M., Lesure, J.F., Halgand, F., Laprévote, O., Edelman, A. Mol. Cell Proteomics (2005) [Pubmed]
  5. Caspase-dependent immunogenicity of doxorubicin-induced tumor cell death. Casares, N., Pequignot, M.O., Tesniere, A., Ghiringhelli, F., Roux, S., Chaput, N., Schmitt, E., Hamai, A., Hervas-Stubbs, S., Obeid, M., Coutant, F., Métivier, D., Pichard, E., Aucouturier, P., Pierron, G., Garrido, C., Zitvogel, L., Kroemer, G. J. Exp. Med. (2005) [Pubmed]
  6. Blocked negative selection of developing T cells in mice expressing the baculovirus p35 caspase inhibitor. Izquierdo, M., Grandien, A., Criado, L.M., Robles, S., Leonardo, E., Albar, J.P., de Buitrago, G.G., Martínez-A, C. EMBO J. (1999) [Pubmed]
  7. Proteinaceous inhibitors of phospholipase A2 purified from inflammatory sites in rats. Suwa, Y., Kudo, I., Imaizumi, A., Okada, M., Kamimura, T., Suzuki, Y., Chang, H.W., Hara, S., Inoue, K. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  8. Glucocorticoid-induced phospholipase A2-inhibitory proteins mediate glucocorticoid teratogenicity in vitro. Gupta, C., Katsumata, M., Goldman, A.S., Herold, R., Piddington, R. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  9. Decreased content of the 35 kDa cytoskeletal protein p35 in Friend erythroleukemia cells exposed to dimethyl sulfoxide and retinoic acid is associated with entrance into a quiescent substrate. Higgins, P.J., Lipkin, M., Bueti, C., Traganos, F. Int. J. Biochem. (1989) [Pubmed]
  10. Attenuation of glucocorticoid functions in an Anx-A1-/- cell line. Croxtall, J.D., Gilroy, D.W., Solito, E., Choudhury, Q., Ward, B.J., Buckingham, J.C., Flower, R.J. Biochem. J. (2003) [Pubmed]
  11. The annexin-1 knockout mouse: what it tells us about the inflammatory response. Roviezzo, F., Getting, S.J., Paul-Clark, M.J., Yona, S., Gavins, F.N., Perretti, M., Hannon, R., Croxtall, J.D., Buckingham, J.C., Flower, R.J. J. Physiol. Pharmacol. (2002) [Pubmed]
  12. Stimulus-dependent specificity for annexin 1 inhibition of the inflammatory nociceptive response: the involvement of the receptor for formylated peptides. Pieretti, S., Di Giannuario, A., De Felice, M., Perretti, M., Cirino, G. Pain (2004) [Pubmed]
  13. Formyl peptide receptors and the regulation of ACTH secretion: targets for annexin A1, lipoxins, and bacterial peptides. John, C.D., Sahni, V., Mehet, D., Morris, J.F., Christian, H.C., Perretti, M., Flower, R.J., Solito, E., Buckingham, J.C. FASEB J. (2007) [Pubmed]
  14. Effective stimulation for IL-12 p35 mRNA accumulation and bioactive IL-12 production of antigen-presenting cells interacted with Th cells. Yamane, H., Kato, T., Nariuchi, H. J. Immunol. (1999) [Pubmed]
  15. Roscovitine: a novel regulator of P/Q-type calcium channels and transmitter release in central neurons. Yan, Z., Chi, P., Bibb, J.A., Ryan, T.A., Greengard, P. J. Physiol. (Lond.) (2002) [Pubmed]
  16. CREB is involved in mouse annexin A1 regulation by cAMP and glucocorticoids. Antonicelli, F., De Coupade, C., Russo-Marie, F., Le Garrec, Y. Eur. J. Biochem. (2001) [Pubmed]
  17. The required role of endogenously produced lipoxin A4 and annexin-1 for the production of IL-10 and inflammatory hyporesponsiveness in mice. Souza, D.G., Fagundes, C.T., Amaral, F.A., Cisalpino, D., Sousa, L.P., Vieira, A.T., Pinho, V., Nicoli, J.R., Vieira, L.Q., Fierro, I.M., Teixeira, M.M. J. Immunol. (2007) [Pubmed]
  18. Aberrant inflammation and resistance to glucocorticoids in annexin 1-/- mouse. Hannon, R., Croxtall, J.D., Getting, S.J., Roviezzo, F., Yona, S., Paul-Clark, M.J., Gavins, F.N., Perretti, M., Morris, J.F., Buckingham, J.C., Flower, R.J. FASEB J. (2003) [Pubmed]
  19. Annexin 1 Negatively Regulates IL-6 Expression via Effects on p38 MAPK and MAPK Phosphatase-1. Yang, Y.H., Toh, M.L., Clyne, C.D., Leech, M., Aeberli, D., Xue, J., Dacumos, A., Sharma, L., Morand, E.F. J. Immunol. (2006) [Pubmed]
  20. Complete structure of the murine p36 (annexin II) gene. Identification of mRNAs for both the murine and the human gene with alternatively spliced 5' noncoding exons. Fey, M.F., Moffat, G.J., Vik, D.P., Meisenhelder, J., Saris, C.J., Hunter, T., Tack, B.F. Biochim. Biophys. Acta (1996) [Pubmed]
  21. Impaired phagocytic mechanism in annexin 1 null macrophages. Yona, S., Heinsbroek, S.E., Peiser, L., Gordon, S., Perretti, M., Flower, R.J. Br. J. Pharmacol. (2006) [Pubmed]
  22. Interactions between the cytoplasmic proteins and the intergenic (promoter) sequence of mouse hepatitis virus RNA: correlation with the amounts of subgenomic mRNA transcribed. Zhang, X., Lai, M.M. J. Virol. (1995) [Pubmed]
  23. In vivo role of caspases in excitotoxic neuronal death: generation and analysis of transgenic mice expressing baculoviral caspase inhibitor, p35, in postnatal neurons. Tomioka, M., Shirotani, K., Iwata, N., Lee, H.J., Yang, F., Cole, G.M., Seyama, Y., Saido, T.C. Brain Res. Mol. Brain Res. (2002) [Pubmed]
  24. Intratumor murine interleukin-12 gene therapy suppressed the growth of local and distant Ewing's sarcoma. Jia, S.F., Duan, X., Worth, L.L., Guan, H., Kleinerman, E.S. Cancer Gene Ther. (2006) [Pubmed]
  25. Purification and characterization of a novel 35-kDa protein from transformed cardiomyocytes. Chandrasekhar, S., Münster, P.N., Henzel, W.A., Daud, A.I. Cell Biol. Int. (1999) [Pubmed]
  26. Post-translational modification plays an essential role in the translocation of annexin A1 from the cytoplasm to the cell surface. Solito, E., Christian, H.C., Festa, M., Mulla, A., Tierney, T., Flower, R.J., Buckingham, J.C. FASEB J. (2006) [Pubmed]
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