Disease relevance of APOBEC2

• ARP-1 is a ubiquitous orphan nuclear receptor that binds to a site (site A) in the apolipoprotein AI (apoAI) liver-specific enhancer and represses its transcriptional activity in hepatoblastoma HepG2 cells [1].
• EXPERIMENTAL DESIGN: PCDGF functions and signaling pathways in dexamethasone-induced apoptosis were studied using a representative dexamethasone-sensitive multiple myeloma cell line ARP-1 [2].

High impact information on APOBEC2

• This element binds to two members of the steroid hormone receptor superfamily of transcription factors produced in enterocytes and Caco-2 cells: hepatic nuclear factor-4 (HNF-4) and apolipoprotein regulatory protein-1 (ARP-1) [3].
• Supplementation of the extracts with purified polypeptides representing fusions between the ARP-1 N- or C-terminal domains and the yeast activator GAL4 DNA binding domain also stimulated transcription from a basal promoter linked to multiple GAL4 DNA binding sites [1].
• We conclude that ARP-1 possesses intrinsic transcription activation potential which is modulated, at least in part, by the intracellular balance of other nuclear receptors that also bind to its cognate DNA binding site [1].
• In in vitro transcription assays, Hela cell nuclear extracts which contain ARP-1 had no effect on transcription from a basal promoter linked to multiple copies of site A [1].
• We conclude that AID and APOBEC2 are likely to be the ancestral members of the AID/APOBEC family (going back to the beginning of vertebrate speciation) with both APOBEC1 and APOBEC3 being mammal-specific derivatives of AID and a complex set of domain shuffling underpinning the expansion and evolution of the primate APOBEC3s [4].

Biological context of APOBEC2

• One of these genes, designated APOBEC2, is found on chromosome 6 [5].
• The promoter region of APOBEC2 contains functional NF-kappaB response elements in the 5' untranslated region of the gene at -625/-616 [6].
• Apolipoprotein B mRNA-editing enzyme catalytic subunit 2 (APOBEC2) is a member of the nucleic-acid-editing enzymes [6].
• ARCD-1 mRNA is ubiquitously expressed; phylogenetic analysis reveals it to be a distant member of the RNA editing family [7].
• Although not competent itself to mediate deamination of apoB mRNA, ARCD-1 inhibits apobec-1-mediated C to U RNA editing [7].

Anatomical context of APOBEC2

• Expression of APOBEC2 is transcriptionally regulated by NF-kappaB in human hepatocytes [6].
• APOBEC-2 mRNA and protein are expressed exclusively in heart and skeletal muscle [8].

Regulatory relationships of APOBEC2

• Inhibition of NF-kappaB activation invariably blocks TNF-alpha-induced APOBEC2 expression [6].

Other interactions of APOBEC2

• APOBEC4 and APOBEC1 are joined in a moderately supported cluster clearly separated from AID, APOBEC2 and APOBEC3 subfamilies [9].
• Recombinant ARCD-1 demonstrates cytidine deaminase and apoB RNA binding activity but does not catalyze C to U RNA editing, either in vitro or in vivo [7].

Analytical, diagnostic and therapeutic context of APOBEC2

• Gene-targeting experiments reveal that both APOBEC2 (despite being an ancestral member of the family with no obvious redundancy in muscle) and APOBEC3 (despite its proposed role in restricting endogenous retrotransposition) are inessential for mouse development, survival, or fertility [10].
• Co-immunoprecipitation assays using ARP-1-selective antibodies revealed specific physical interactions between ARP-1 and the basal transcription factor TFIIB [1].
• PURPOSE: To establish a method for the recording of multifocal electroretinograms (MF-ERGs) in animals under fundus control using a scanning-laser ophthalmoscope (SLO) and to analyze the spatial distribution of disease in a strain of Abyssinian cats with a recessively inherited rod-cone degeneration (ARCD) [11].

References