Annexin 1: the new face of an old molecule

Abstract

The annexin superfamily consists of 13 calcium or calcium and phospholipid binding proteins with a significant degree of biological and structural homology (40-60%). First described in the late 1970s and subsequently referred to as macrocortin, renocortin, lipomodulin, lipocortin-1, and more recently Annexin 1, this 37 kDa calcium and phospholipid binding protein is a strong inhibitor of glucocorticoid-induced eicosanoid synthesis and PLA2. Recent interest in the biological activity of this intriguing molecule has unraveled important functional attributes of Annexin 1 in a variety of inflammatory pathways, on cell proliferation machinery, in the regulation of cell death signaling, in phagocytic clearance of apoptosing cells, and most importantly in the process of carcinogenesis. Here we attempt to present a short review on these diverse biological activities of an interesting and important molecule, which could be a potential target for novel therapeutic intervention in a host of disease states.

Annexin-1 interacts with NEMO and RIP1 to constitutively activate IKK complex and NF-κB: implication in breast cancer metastasis

“…The expression of ANXA1 has been studied in many types of cancer; however, there is no consensus on the role of this protein in tumor initiation and/or progression. ANXA1 has been reported to be reduced or lost in many cancers (Lim and Pervaiz, 2007). In breast cancer, however, reports are conflicting, where ANXA1 expression has been shown to be increased in some ductal carcinomas (Ahn et al, 1997;Pencil and Toth, 1998), but we and others have recently reported a loss of ANXA1 in breast carcinomas (Shen et al, 2006;Cao et al, 2008;Ang et al, 2009).…”

“…In particular, Annexin-1 (ANXA1) is anti-inflammatory, anti-proliferative and pro-apoptotic, and regulates differentiation (Flower and Rothwell, 1994;Perretti and Gavins, 2003;Parente and Solito, 2004;Lim and Pervaiz, 2007). The expression of ANXA1 has been studied in many types of cancer; however, there is no consensus on the role of this protein in tumor initiation and/or progression.…”

Anti-inflammatory functions of glucocorticoid-induced genes

“…AnxA1 was first identified as a factor that was released from GC-stimulated cells in vitro or in vivo, and exerted anti-inflammatory effects mirroring those of GCs. Most notably it inhibited release of proinflammatory prostaglandins, and impaired leukocyte extravasation at sites of inflammation (Chatterjee et al, 2005;de Coupade et al, 2003;Gavins et al, 2003;Lim and Pervaiz, 2007;Liu et al, 2005;Parente and Solito, 2004). AnxA1 is relocalized from the cytoplasm to the plasma membrane in response to a variety of agonists including GCs, and can be externalized or secreted via an uncharacterized mechanism.…”

Characterisation and protein expression profiling of annexins in colorectal cancer

“…The annexins are classified into five groups (A -E), and within each of these groups, individual annexins are identified numerically. Annexins in group A are human annexins, with group B referring to animal annexins without human orthologs, group C to fungi and moulds, group D to plants and group E to protists (Liemann and Huber, 1997;Rand, 2000;Hayes and Moss, 2004;Rescher and Gerke, 2004;Lim and Pervaiz, 2007). The characteristic annexin structural motif is a 70-amino-acid repeat, called the annexin repeat.…”

“…This binding can be reversed by the removal of calcium, freeing the annexin from the phospholipid membrane. However, the functional significance of their reversible membrane-binding ability remains unknown in many annexins, although in some it is thought to be important for vesicle aggregation and membrane organisation (Liemann and Huber, 1997;Rand, 2000;Rescher and Gerke, 2004;Lim and Pervaiz, 2007). Although all annexins share this binding property, there is variation in calcium sensitivity and phospholipid specificity between individual annexins.…”