Annexin A1

Annexin A1

PDB rendering based on 1ain.
Identifiers
Symbols ANXA1; ANX1; LPC1
External IDs OMIM151690 MGI96819 HomoloGene563 GeneCards: ANXA1 Gene
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 301 16952
Ensembl ENSG00000135046 ENSMUSG00000024659
UniProt P04083 Q3U5N9
RefSeq (mRNA) NM_000700.1 NM_010730.2
RefSeq (protein) NP_000691.1 NP_034860.2
Location (UCSC) Chr 9:
75.77 – 75.79 Mb
Chr 19:
20.45 – 20.47 Mb
PubMed search [1] [2]

Annexin A1 also known as lipocortin I is a protein that in humans is encoded by the ANXA1 gene.[1]

Contents

Function

Annexin I belongs to the annexin family of Ca2+-dependent phospholipid-binding proteins that have a molecular weight of approximately 35,000 to 40,000 and are preferentially located on the cytosolic face of the plasma membrane. Annexin I protein has an apparent relative molecular mass of 40 kDa, with phospholipase A2 inhibitory activity.[2]

Clinical significance

Inflammation

Since phospholipase A2 is required for the biosynthesis of the potent mediators of inflammation, prostaglandins, and leukotrienes, annexin I may have potential anti-inflammatory activity.[2]

Glucocorticoids stimulate production of lipocortin.[3] In this way, synthesis of eicosanoids are inhibited.

Cancer

Annexin I has been of interest for use as a potential anticancer drug. Upon induction by modified NSAIDS and other potent anti-inflammatory drugs, annexin I inhibits the NF-κB signal transduction pathway, which is exploited by cancerous cells to proliferate and avoid apoptosis. ANXA1 inhibits the activation of NF-κB by binding to the p65 subunit.[4]

Leukemia

The gene for annexin A1 (ANXA1) is upregulated in hairy cell leukemia. ANXA1 protein expression is specific to hairy cell leukemia. Detection of ANXA1 (by immunocytochemical means) reportedly provides a simple, highly-sensitive and specific assay for the diagnosis of hairy cell leukemia.[5]

Breast cancer

Exposure of MCF-7 breast cancer cells to high physiological levels (up to 100 nM) of estrogen lead to an up-regulation of annexin-1 expression partially through the activation of CREB, and dependent on activation of the estrogen receptor alpha. Treatment of MCF-7 cells with physiological levels of estrogen (1 nM) induced proliferation while high pregnancy levels of estrogen (100 nM) induced a growth arrest of MCF-7 cells. Silencing of ANXA1 with specific siRNA reverses the estrogen-dependent proliferation as well as growth arrest. ANXA1 is lost in clinical breast cancer, indicating that the anti-proliferative protective function of ANXA1 against high levels of estrogen may be lost in breast cancer. This data suggests that ANXA1 may act as a tumor suppressor gene and modulate the proliferative functions of estrogens.[6]

Annexin-A1 has also been shown to be protective against DNA damage induced by heat in breast cancer cells, adding to the evidence that it has tumor suppressive and protective activities. When ANXA1 is silenced or lost in cancer, cells are more prone to DNA damage, indicating its unidentified diverse role in genome maintenance or integrity.[7]

References

  1. ^ Wallner BP, Mattaliano RJ, Hession C, Cate RL, Tizard R, Sinclair LK, Foeller C, Chow EP, Browing JL, Ramachandran KL (1986). "Cloning and expression of human lipocortin, a phospholipase A2 inhibitor with potential anti-inflammatory activity". Nature 320 (6057): 77–81. doi:10.1038/320077a0. PMID 2936963. 
  2. ^ a b "Entrez Gene: ANXA1 annexin A1". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=301. 
  3. ^ Peers SH, Smillie F, Elderfield AJ, Flower RJ (January 1993). "Glucocorticoid-and non-glucocorticoid induction of lipocortins (annexins) 1 and 2 in rat peritoneal leucocytes in vivo". British journal of pharmacology 108 (1): 66–72. PMC 1907693. PMID 8428216. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1907693. 
  4. ^ Zhang Z, Huang L, Zhao W, Rigas B (March 2010). "Annexin 1 induced by anti-inflammatory drugs binds to NF-kappaB and inhibits its activation: anticancer effects in vitro and in vivo". Cancer Res. 70 (6): 2379–88. doi:10.1158/0008-5472.CAN-09-4204. PMC 2953961. PMID 20215502. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2953961. 
  5. ^ Falini B, Tiacci E, Liso A, Basso K, Sabattini E, Pacini R, Foa R, Pulsoni A, Dalla Favera R, Pileri S (June 2004). "Simple diagnostic assay for hairy cell leukaemia by immunocytochemical detection of annexin A1 (ANXA1)". Lancet 363 (9424): 1869–70. doi:10.1016/S0140-6736(04)16356-3. PMID 15183626. 
  6. ^ Ang EZ, Nguyen HT, Sim HL, Putti TC, Lim LH (February 2009). "Annexin-1 regulates growth arrest induced by high levels of estrogen in MCF-7 breast cancer cells". Mol. Cancer Res. 7 (2): 266–74. doi:10.1158/1541-7786.MCR-08-0147. PMID 19208747. 
  7. ^ Nair S, Hande MP, Lim LH (August 2010). "Annexin-1 protects MCF7 breast cancer cells against heat-induced growth arrest and DNA damage". Cancer Lett. 294 (1): 111–7. doi:10.1016/j.canlet.2010.01.026. PMID 20163912. 

Further reading

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.