Dimeric structure of a human apolipoprotein B mRNA editing protein and cloning and chromosomal localization of its gene.

Lau, Paul P.; Zhu, Hui; Baldini, Antonio; Charnsangavej, Chutaporn; Chan, Lawrence

doi:10.1073/pnas.91.18.8522

Cited by 133 publications

(128 citation statements)

References 32 publications

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“…In humans, only in small intestine the APOBEC-1 mRNA is expressed to levels that are clearly detectable by Northern blotting (Lau et al, 1994). A survey in several fetal, postnatal and adult human tissues demonstrated a more widespread tissue expression of apo B mRNA editing in humans (Teng et al, 1990).…”

Section: Discussionmentioning

confidence: 99%

Absence of APOBEC-1 mediated mRNA editing in human carcinomas

et al. 1999

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The transgene expression of the catalytic subunit APOBEC-1 of the apo B mRNA editing enzymecomplex can cause hepatocellular carcinoma in mice and rabbits. It has been proposed that aberrant editing of mRNA may represent a novel oncogenic principle. This investigation aimed to de®ne whether such aberrant hyperediting mediated by APOBEC-1 occurs in human carcinomas. Editing and hyperediting of apo B, NAT1 or NF1 mRNA was not identi®ed in any of 28 resected tumor specimens, including hepatocellular, bile duct, gastric, colorectal, pancreatic adeno-and neuroendocrine, lung adeno-, medullary thyroid and breast carcinoma, soft tissue sarcoma and neuroblastoma. In most types of carcinoma, signi®cant levels for full-length APOBEC-1 mRNA could not be detected. Low level expression of APOBEC-1 was found in colorectal and gastric carcinoma where most of the APOBEC-1 mRNA is inactivated by alternate splicing. The`auxiliary' components of the apo B mRNA editing enzyme-complex are missing in many tumors including colorectal and gastric carcinoma, but are highly expressed in hepatocellular, lung adeno-and breast carcinoma all of which lack APOBEC-1. Taken together, either APOBEC-1 or the`auxiliary' components of the apo B mRNA editing enzyme-complex or both are missing in human carcinomas resulting in the absence of mRNA editing. Currently, there is no evidence that aberrant editing mediated by APOBEC-1 contributes to the tumorigenesis of natural human carcinomas.

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Section: Discussionmentioning

confidence: 99%

Absence of APOBEC-1 mediated mRNA editing in human carcinomas

et al. 1999

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“…AID dimerization through the β2 strand has been proposed based on the structure of A2 33 . We tested the effect of perturbing the predicted AID β2, residues [40][41][42][43][44][45][46][47][48][49][50][51][52][53] in our model, on oligomerization by introducing one (F46A), two (F46A/Y48A) 33 or four (F46A/Y48A/R50G/N51A, named AID FYRN) mutations. The ability of each of these mutants to interact with wt AID was monitored by comparing their efficiency in coimmunoprecipitating with AID-Flag.…”

Section: Aid Has a Conformational Positively Charged Nlsmentioning

confidence: 99%

“…The stoichiometry and architecture of the biologically relevant AID molecule is unknown but many indirect evidences suggest that it will have quaternary structure 33,35,42,47,48 as all cytidine deaminases including the APOBECs do 33,49,50 . Predicting AID dimerization through β2 (ref.…”

Section: Active Nuclear Import Of Aidmentioning

confidence: 99%

Active nuclear import and cytoplasmic retention of activation-induced deaminase

Patenaude

Orthwein

et al. 2009

Nat Struct Mol Biol

134

175

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The enzyme Activation Induced Deaminase (AID) triggers antibody diversification in B-cells by catalyzing deamination and consequently mutation of immunoglobulin genes. To minimize off-target deamination, AID is restrained by several regulatory mechanisms including nuclear exclusion, thought to be mediated exclusively by active nuclear export. Here we identify two other mechanisms involved in controlling AID subcellular localization. AID is unable to passively diffuse into the nucleus, despite its small size, its nuclear entry requiring active import mediated by a conformational nuclear localization sequence (NLS). We also identify a determinant for AID cytoplasmic retention in its Cterminus, which hampers diffusion to the nucleus, competes with nuclear import and is critical for maintaining the predominantly cytoplasmic localization of AID in steady-state conditions. Blocking nuclear import alters the balance between these processes in favor of cytoplasmic retention, resulting in reduced isotype class switching.3

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“…A multiple protein editosome catalyses and regulates editing of C'''' [11,22,26]. The components of the minimal editosome from defined in itro system analyses are APOBEC-1 as a homodimeric cytidine deaminase [28] bound to the auxiliary protein ACF\ASP that serves as the editing-site recognition factor through its mooringsequence-selective RNA-binding activity [30,31]. Several other auxiliary protein candidates have also been described that had binding affinities for APOBEC-1 and\or apoB mRNA and that demonstrated the ability to modulate editing efficiency [23,24,26,31,33,34,37,38].…”

Section: Discussionmentioning

confidence: 99%

“…Editosome assembly in cells [22,26] or in itro [11,15,22,27] required a complex protein composition with an aggregate size of 27 S. Minimally, in itro editing activity required a homodimer of APOBEC-1 (catalytic subunit for cytidine-to-uridine editing of apolipoprotein B mRNA-1), the zinc-dependent catalytic subunit of cytidine deaminase [28,29] and a 65 kDa RNA binding protein, ACF\ASP (APOBEC-1 complementation factor\APOBEC-1 stimulatory protein) [30,31]. APOBEC-1 demonstrated a weak and non-specific RNA binding activity to AU-rich apoB sequences [32] and alone could not edit apoB mRNA.…”

Section: Introductionmentioning

confidence: 99%

Commitment of apolipoprotein B RNA to the splicing pathway regulates cytidine-to-uridine editing-site utilization

Sowden

Smith

2001

Biochemical Journal

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A tripartite motif located in the centre of the 7.5 kb exon 26 of apolipoprotein B (apoB) mRNA directs editosome assembly and site-specific cytidine-to-uridine editing at nucleotide 6666. apoB mRNA editing is a post-transcriptional event, occurring primarily at the time exon 26 is spliced or at a time after splicing, but before nuclear export. We show, through reporter RNA constructs, that RNA splice sites suppress editing of precursor RNAs when placed proximal or distal to the editing site. Processed RNAs were edited more efficiently than precursor RNAs. Mutation of both the splice donor and acceptor sites was necessary for RNAs to be edited efficiently. The results suggested that commitment of pre-mRNA to the splicing and\or nuclear-

show abstract

Dimeric structure of a human apolipoprotein B mRNA editing protein and cloning and chromosomal localization of its gene.

Abstract: ABSTRACThomopolymers. The fact that the apoB mRNA editing protein also exists as a homodimer has important implications for the mechanism of apoB mRNA editing in humans.

Cited by 133 publications

References 32 publications

Absence of APOBEC-1 mediated mRNA editing in human carcinomas

Absence of APOBEC-1 mediated mRNA editing in human carcinomas

Active nuclear import and cytoplasmic retention of activation-induced deaminase

Commitment of apolipoprotein B RNA to the splicing pathway regulates cytidine-to-uridine editing-site utilization

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