Disease relevance of ANXA7

• These include the first single-domain, bacterial annexin in Cytophaga hutchinsonii, the 21 tetrad annexins from the unicellular protist Giardia intestinalis, an ancestor to land plant annexins from the green alga Ostreococcus lucimarinus, invertebrate octad annexins and a critical polymorphism in human ANXA7 [1].
• We conclude that the ANX7 gene exhibits many biological and genetic properties expected of a TSG and may play a role in prostate cancer progression [2].
• An in vitro study of astrocyte-derived C6 rat glioblastoma cells expressing a GFP tagged annexin VII fusion protein demonstrates a sequential redistribution of the fusion protein in response to rising intracellular Ca2+ concentrations [3].
• HIV-1 Gag shares a signature motif with annexin (Anx7), which is required for virus replication [4].
• CONCLUSIONS: High levels of ANX7 in tumor correlate strongly with poor survival of HER2-negative patients and the most aggressive forms of breast cancer [5].

High impact information on ANXA7

• Annexin 7 (ANX7) acts as a tumor suppressor gene in prostate cancer, where loss of heterozygosity and reduction of ANX7 protein expression is associated with aggressive metastatic tumors [6].
• ANX7, a candidate tumor suppressor gene for prostate cancer [2].
• The microsatellite marker closest to the ANX7 locus showed the highest rate of LOH, including one homozygous deletion [2].
• The ANX7 gene is located on human chromosome 10q21, a site long hypothesized to harbor a tumor suppressor gene(s) (TSG) associated with prostate and other cancers [2].
• Here we report that human tumor cell proliferation and colony formation are markedly reduced when the wild-type ANX7 gene is transfected into two prostate tumor cell lines, LNCaP and DU145 [2].

Chemical compound and disease context of ANXA7

• Distinct Effects of Annexin A7 and p53 on Arachidonate Lipoxygenation in Prostate Cancer Cells Involve 5-Lipoxygenase Transcription [7].

Biological context of ANXA7

• 4. Overlay assays using deletion constructs of the synexin N-terminal domain mapped the sorcin binding site to the N-terminal 31 amino acids of the synexin protein [8].
• Furthermore, synexin down-regulation abolished anti-apoptotic activity of galectin-3 [9].
• Taken together, these results suggest that synexin mediates galectin-3 translocation to the perinuclear mitochondrial membranes, where it regulates mitochondrial integrity critical for apoptosis regulation [9].
• Thus, ANXA7 and p53 can distinctly regulate LOX transcription that is potentially relevant to the AA-mediated cell growth control in tumor suppression [7].
• Synexin is a calcium-dependent membrane binding protein that not only fuses membranes but also acts as a voltage-dependent calcium channel [10].

Anatomical context of ANXA7

• Additionally, synexin forms a complex with sorcin and recruits this protein to chromaffin granule membranes in a Ca2+-dependent manner [8].
• Galectin-3 translocates to the perinuclear membranes and inhibits cytochrome c release from the mitochondria. A role for synexin in galectin-3 translocation [9].
• Cell fractionation studies indicated that annexin VII is equally distributed between cytosol and membrane fractions in undifferentiated cells, while in differentiated cells it is exclusively present in the membrane fraction [11].
• Annexin VII exists in a 47 kDa and a 51 kDa isoform with the 51 kDa protein being the only isoform present in skeletal muscle [11].
• Expression and localisation of annexin VII (synexin) isoforms in differentiating myoblasts [11].

Associations of ANXA7 with chemical compounds

• Synexin, a Ca(2+)- and phospholipid-binding protein, was one of the proteins identified [9].
• We confirmed direct interaction between galectin-3 and synexin by glutathione S-transferase pull-down assay in vitro [9].
• By sucrose gradient centrifugation of postnuclear supernatants we identified two distinct annexin VII-containing membrane populations that cofractionated with caveolin 3- and sorcin-containing membranes [11].
• Because ANXA7-caused liposome aggregation can be promoted by arachidonic acid (AA), we hypothesized that the phospholipid-binding tumor suppressor ANXA7 is associated with AA cascade [7].
• However, as with synexin, the dihydropyridine Ca2+ channel antagonist nifedipine does not affect endonexin II channel activity [12].

Other interactions of ANXA7

• Affinity chromatography using this construct identified sorcin as a Ca2+-dependent synexin-binding protein [8].
• Stomatin is the major protein of the microvesicular lipid rafts, whereas synexin and sorcin represent the major proteins of the nanovesicular rafts in the presence of Ca(++) [13].
• The human synexin (annexin VII) gene occurs as a single copy at chromosome 10q21.1-21.2 and substantially deviates in size and in the location of splice junctions from the other two well-characterized members of the annexin gene family, lipocortin I (annexin I) and calpactin I (annexin II) [14].
• The identities of PKC, annexin I, annexin IV, annexin VI, and annexin VII were confirmed by Western blotting [15].
• Voltage dependent binding of annexin V, annexin VI and annexin VII-core to acidic phospholipid membranes [16].

Analytical, diagnostic and therapeutic context of ANXA7

• Both in undifferentiated and differentiated cells annexin VII was localized by immunofluorescence microscopy to punctate structures which were distributed all over the cell [11].
• We have analyzed 90 degree light scattering data to determine a titration curve for the activation of synexin by Ca2+ in the self-association reaction [17].
• Electron microscopy of negatively stained samples reveals that synexin monomers associate to form 50 A by 150 A rods which in turn associate side to side and end to end to form bundles of parallel rods [17].
• After subtotal nephrectomy protein excretion SNX (130.0 +/- 22.5 mg/24 h) was increased in comparison to the ET(A)-group (446 +/- 103 mg/24 h) and the ET(AB)-group (23.2 +/- 37 mg/24 h) vs sham: 115 +/- 19 mg/24 h) [18].
• SNX is attached to genomic DNA with a simultaneous ligation/restriction reaction that is highly efficient and improves recovery of sequences after subtractive hybridization [19].

References