Disease relevance of ANXA8

• In acute promyelocytic leukemia (APL) the annexin VIII gene is highly expressed, but its expression is undetectable in the blasts of other acute leukemias [1].
• Expression of the annexin VIII gene in all other leukemias, including acute myelogenous leukemia, chronic myelogenous leukemia, chronic lymphocytic leukemia, and acute lymphoblastic leukemia, was undetectable, except in one patient with acute myelogenous leukemia in which a very low level of expression was detected [2].
• In line with these characteristics annexin A8 is recruited to F-actin-associated PtdIns(4,5)P(2)-rich membrane domains formed in HeLa cells upon infection with non-invading enteropathogenic Escherichia coli [3].
• Annexin VIII mRNA was found to be specifically expressed in acute promyelocytic leukemia (APL) cells; it was not found in other types of acute myeloid leukemia (AML) nor in lymphoid malignancies [4].
• Annexin VIII was originally found to be a vascular anticoagulant, but evidence obtained from our recent studies suggests that it does not play a role in hemorrhage diathesis in APL [5].

High impact information on ANXA8

• The F-5 cDNA was identified as a portion of ANNEXIN VIII, whose product was expressed in promyelocytic leukemia cells and UOC-B1 cells, but not in other leukemic cell lines [6].
• Regulation of the expression of annexin VIII in acute promyelocytic leukemia [1].
• These results indicated that annexin VIII is predominantly localized to the plasma membrane [1].
• The plasma membrane localization and its property as a phospholipase inhibitor suggests that annexin VIII may have a role in the signal transduction pathway in the APL cells [1].
• The half-life of the annexin VIII mRNA is about 5 to 6 hours, as determined by using actinomycin D as a transcription inhibitor [1].

Biological context of ANXA8

• Vascular anticoagulant beta: a novel human Ca2+/phospholipid binding protein that inhibits coagulation and phospholipase A2 activity. Its molecular cloning, expression and comparison with VAC-alpha [7].
• The annexin VIII gene was assigned to chromosome 10, which indicates that specific expression of this gene in APL is not directly involved in the t(15;17) breakpoint region [2].
• The annexin VIII is neither an extracellular protein nor associated with the cell surface suggesting that it does not play a role in blood coagulation in vivo [1].
• DNA sequence analysis of pRD1 showed that this gene is similar to the DNA sequence of annexin VIII, a gene which encodes a vascular anticoagulant [2].
• The greatest similarity in amino acid sequence was observed with annexin VIII (VAC-beta) [8].

Anatomical context of ANXA8

• In the tongue epithelium as well, ANXA8 protein was found in suprabasal layers [9].
• ANXA8 immunoreactivity was also found in suprabasal layers of the stratified epithelia of the oesophagus and the forestomach, while it was detected in all layers of the cornea epithelium and in the cornea endothelium of the eye [9].
• Its location in the suprabasal layers suggests that ANXA8 may be associated with the terminal differentiation of epithelial cells in these tissues [9].
• Annexin VIII is highly expressed in the APL cell line, NB4 [2].
• All cell types expressed Annexin V whereas only HeLa cells had detectable levels of Annexin VIII [10].

Associations of ANXA8 with chemical compounds

• In the present investigation, we showed using the APL-derived NB4 cell line that expression of the annexin VIII gene is regulated at the transcription level during induced differentiation by all-trans retinoic acid (ATRA) [1].
• Treatment of NB-4 cells with all-trans retinoic acid (ATRA) or the phorbol ester TPA induced terminal differentiation and down-regulated annexin VIII mRNA expression rapidly within a few hours; vitamin D3 was ineffective in this regard; the protein kinase C activator Bryostatin 1 up-regulated the expression [4].

Regulatory relationships of ANXA8

• Antiserum raised against VAC-beta weakly cross-reacts with VAC-alpha [7].

Other interactions of ANXA8

• Due to its 56% identity to the human vascular anticoagulant (VAC) the new protein is named VAC-beta, renaming the previous VAC as VAC-alpha [7].
• Therefore, dysregulation of the RARA gene may be related to the overexpression of annexin VIII in APL [2].
• Contrarily, genes involved in epidermal differentiation complex such as S100A9 and ANXA8 were upregulated in SC [11].
• Specific expression of the annexin VIII gene in acute promyelocytic leukemia [2].
• The crystal structure of annexin A8 is similar to that of annexin A3 [12].

Analytical, diagnostic and therapeutic context of ANXA8

• Genomic Southern blot analysis shows a VAC-beta gene of comparable complexity to the VAC-alpha gene [7].
• Western blot analyses using a murine ANXA8-specific antiserum showed, that the 36 kD ANXA8 protein was most abundant in the skin and tongue [9].
• A multiple tissue Northern blot analysis was performed, and we found that annexin VIII is normally expressed in the placenta and the lung [1].
• Cellular localization of the annexin VIII protein was determined by immunofluorescence staining and subcellular fractionation [1].
• A 36 kDa calcium/phospholipid binding protein in human placenta was identified as VAC-beta (annexin-8) by a combination of immunological and peptide mapping analyses [13].

References