Diverse molecular functions of aspartate β‑hydroxylase in cancer (Review)

Abstract

Aspartate/asparagine β-hydroxylase (AspH) is a type II transmembrane protein that catalyzes the post-translational hydroxylation of definite aspartyl and asparaginyl residues in epidermal growth factor-like domains of substrates. In the last few decades, accumulating evidence has indicated that AspH expression is upregulated in numerous types of human malignant cancer and is associated with poor survival and prognosis. The AspH protein aggregates on the surface of tumor cells, which contributes to inducing tumor cell migration, infiltration and metastasis. However, small-molecule inhibitors targeting hydroxylase activity can markedly block these processes, both in vitro and in vivo . Immunization of tumor-bearing mice with a phage vaccine fused with the AspH protein can substantially delay tumor growth and progression. Additionally, AspH antigen-specific CD4 + and CD8 + T cells were identified in the spleen of tumor-bearing mice. Therefore, these agents may be used as novel strategies for cancer treatment. The present review summarizes the current progress on the underlying mechanisms of AspH expression in cancer development.

Ethanol consumption during gestation promotes placental alterations in IGF-1 deficient mice

“…Also of note, although there is no information on other proteins that regulate AAH in the placenta, there are other protein entities that modulate its expression and would be interesting to evaluate. 47 IGF-1 plays a crucial role in placental and fetal development through binding to its putative receptor (IGF1R). Also, IGF-1 can bind to IGF-2 receptor (IGF2R) or to insulin receptor (INSR), but with lower affinity.…”

Labyrinthin: A distinct pan-adenocarcinoma diagnostic and immunotherapeutic tumor specific antigen

“…TAAs are generally normal occurring proteins that are overexpressed in cancers as either a marker and/or a contributor to tumorigenesis, as is the case with epidermal growth factor receptor 2 (i.e., HER2) or androgen receptors in prostate cancer [8]. In recent years, aspartate/asparagine β-hydroxylase (ASPH), which is present in the cytosol of cells from a wide variety of tissues (The Human Protein Atlas), has also been ascribed as a TAA that is overexpressed in various cancers [9,10,11] .…”

Fluorinated derivatives of pyridine-2,4-dicarboxylate are potent inhibitors of human 2-oxoglutarate dependent oxygenases

“…The development of potent and selective inhibitors for 2OG hydroxylases other than the PHDs is of basic scientific (for use in functional assignment studies) and therapeutic interest, in the latter case for diseases including cancer [4] . For example, aspartate/asparagine-β-hydroxylase (AspH), which catalyzes the stereoselective C3 hydroxylation of Asp/Asn-residues that are part of specific disulfide isomers of epidermal growth factor-like domains (EGFDs) [5] , [6] , [7] , and certain JmjC lysine-specific N ε -demethylases, which catalyze the N ε -lysine demethylation of histones via initial N ε -methyl-group hydroxylation followed by fragmentation to give formaldehyde as a coproduct (Supporting Figure S1), are current medicinal chemistry targets for cancer treatment [8] , [9] , [10] , [11] , [12] .

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