Functions and regulation of the APOBEC family of proteins

Smith, Harold C.; Bennett, Ryan P.; Kizilyer, Ayse; McDougall, William M.; Prohaska, Kimberly M.

doi:10.1016/j.semcdb.2011.10.004

Cited by 187 publications

(191 citation statements)

References 147 publications

Supporting

Mentioning

189

Contrasting

Unclassified

Order By: Relevance

“…(m) and (p) refer to maternal and paternal ko/+ heterozygosity, respectively. Several considerations are relevant: We found a TGCT prevalence of 31.5% in Ter/+ control males on the 129S1/SvImJ background, which represents a significant increase (P < 10 −5 ) compared with the published values (30,38,39). However, the previous studies were performed with a different 129 substrain (129T1/Sv).…”

Section: Transgenerational Interactions Between Apobec1 Ko and Dnd1 Termentioning

confidence: 71%

“…Dnd1 shares sequence similarity with Apobec1 complementation factor (A1cf) (36), the RNA-binding component of the ApoB RNAediting complex (37,38). This similarity raises the possibility that DND1, like A1CF, functions in RNA editing and in turn that RNA-editing mutants affect TGCT susceptibility.…”

mentioning

confidence: 99%

“…This similarity raises the possibility that DND1, like A1CF, functions in RNA editing and in turn that RNA-editing mutants affect TGCT susceptibility. Apobec1 encodes a cytidine deaminase, which is the catalytic component of the ApoB RNA-editing complex (37,38). Recent evidence suggests that several deaminases in the Apobec1 family also have DNA demethylase activity (39)(40)(41).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Transgenerational epigenetic effects of theApobec1cytidine deaminase deficiency on testicular germ cell tumor susceptibility and embryonic viability

Nelson

Heaney

Tesar

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Environmental agents and genetic variants can induce heritable epigenetic changes that affect phenotypic variation and disease risk in many species. These transgenerational effects challenge conventional understanding about the modes and mechanisms of inheritance, but their molecular basis is poorly understood. The Deadend1 (Dnd1) gene enhances susceptibility to testicular germ cell tumors (TGCTs) in mice, in part by interacting epigenetically with other TGCT modifier genes in previous generations. Sequence homology to A1cf, the RNA-binding subunit of the ApoB editing complex, raises the possibility that the function of Dnd1 is related to Apobec1 activity as a cytidine deaminase. We conducted a series of experiments with a genetically engineered deficiency of Apobec1 on the TGCT-susceptible 129/Sv inbred background to determine whether dosage of Apobec1 modifies susceptibility, either alone or in combination with Dnd1, and either in a conventional or a transgenerational manner. In the paternal germ-lineage, Apobec1 deficiency significantly increased susceptibility among heterozygous but not wild-type male offspring, without subsequent transgenerational effects, showing that increased TGCT risk resulting from partial loss of Apobec1 function is inherited in a conventional manner. By contrast, partial deficiency in the maternal germ-lineage led to suppression of TGCTs in both partially and fully deficient males and significantly reduced TGCT risk in a transgenerational manner among wild-type offspring. These heritable epigenetic changes persisted for multiple generations and were fully reversed after consecutive crosses through the alternative germ-lineage. These results suggest that Apobec1 plays a central role in controlling TGCT susceptibility in both a conventional and a transgenerational manner.epigenetics | testicular cancer | gametogenesis | epistasis E stablishing the genetic basis and mode of inheritance for most traits and diseases has proven to be remarkably elusive (1). Susceptibility to testicular germ cell tumors (TGCTs) is illustrative (2). Testicular cancer is the most common malignancy affecting young men (3), more than 90% of testicular cancers result from TGCTs (4), TGCTs rank third in heritability among all cancers (5), and family history is the strongest known risk factor with a two-to sixfold increase among sons and a 5-to 19-fold increase among brothers of affected individuals (6-9). Despite the strong evidence for heritability, the only TGCT susceptibility factors identified in genome-wide association studies are the gr/gr deletion on the Y chromosome and autosomal variants in KITLG, SPRY4, BAK1, and DMRT1, which together account for less than 10% of risk (10-14). The substantial difference in prevalence between sons and brothers of cases and the epidemiological evidence for maternal estrogens, birth order, birth weight, and other factors (15-17) together raise the possibility that maternal conditions, epigenetic effects, and perhaps unconventional modes of inheritance also contribute to TG...

show abstract

Section: Transgenerational Interactions Between Apobec1 Ko and Dnd1 Termentioning

confidence: 71%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Transgenerational epigenetic effects of theApobec1cytidine deaminase deficiency on testicular germ cell tumor susceptibility and embryonic viability

Nelson

Heaney

Tesar

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…4 Recoding RNA editing by cytidine deamination was thought to be rare in humans, physiologically occurring only in the APOB RNA in intestinal cells mediated by the APOBEC1 cytidine deaminase enzyme. 5 We recently found that transcripts of hundreds of genes coordinately acquire site-specific C-to-U (C > U) RNA editing in peripheral blood monocytes that are exposed to hypoxia and during M1 (proinflammatory) macrophage differentiation. 6 This editing predicts protein recoding in dozens of genes.…”

mentioning

confidence: 99%

Transient overexpression of exogenous APOBEC3A causes C-to-U RNA editing of thousands of genes

et al. 2016

View full text Add to dashboard Cite

APOBEC3A cytidine deaminase induces site-specific C-to-U RNA editing of hundreds of genes in monocytes exposed to hypoxia and/or interferons and in pro-inflammatory macrophages. To examine the impact of APOBEC3A overexpression, we transiently expressed APOBEC3A in HEK293T cell line and performed RNA sequencing. APOBEC3A overexpression induces C-to-U editing at more than 4,200 sites in transcripts of 3,078 genes resulting in protein recoding of 1,110 genes. We validate recoding RNA editing of genes associated with breast cancer, hematologic neoplasms, amyotrophic lateral sclerosis, Alzheimer disease and primary pulmonary hypertension. These results highlight the fundamental impact of APOBEC3A overexpression on human transcriptome by widespread RNA editing.

show abstract

“…This family is composed of eleven known members: APOBEC1, APOBEC2, APOBEC3 (further classified as A3A to A3H), APOBEC4, and AID (activation induced deaminase). APOBEC proteins are associated with several functions involving editing of DNA or RNA (reviewed by Smith et al 1 ). APOBEC1 mediates deamination of cytidine at position 6666 of apolipoprotein B mRNA, resulting in the introduction of a premature stop codon and the production of the short form of the protein 2– 4 .…”

Section: Introductionmentioning

confidence: 99%

A putative antiviral role of plant cytidine deaminases

et al. 2017

View full text Add to dashboard Cite

Background: A mechanism of innate antiviral immunity operating against viruses infecting mammalian cells has been described during the last decade. Host cytidine deaminases ( e.g., APOBEC3 proteins) edit viral genomes, giving rise to hypermutated nonfunctional viruses; consequently, viral fitness is reduced through lethal mutagenesis. By contrast, sub-lethal hypermutagenesis may contribute to virus evolvability by increasing population diversity. To prevent genome editing, some viruses have evolved proteins that mediate APOBEC3 degradation. The model plant Arabidopsis thaliana genome encodes nine cytidine deaminases ( AtCDAs), raising the question of whether deamination is an antiviral mechanism in plants as well. Methods: Here we tested the effects of expression of AtCDAs on the pararetrovirus Cauliflower mosaic virus (CaMV). Two different experiments were carried out. First, we transiently overexpressed each one of the nine A. thaliana AtCDA genes in Nicotiana bigelovii plants infected with CaMV, and characterized the resulting mutational spectra, comparing them with those generated under normal conditions. Secondly, we created A. thaliana transgenic plants expressing an artificial microRNA designed to knock-out the expression of up to six AtCDA genes. This and control plants were then infected with CaMV. Virus accumulation and mutational spectra where characterized in both types of plants. Results: We have shown that the A. thaliana AtCDA1 gene product exerts a mutagenic activity, significantly increasing the number of G to A mutations in vivo, with a concomitant reduction in the amount of CaMV genomes accumulated. Furthermore, the magnitude of this mutagenic effect on CaMV accumulation is positively correlated with the level of AtCDA1 mRNA expression in the plant. Conclusions: Our results suggest that deamination of viral genomes may also work as an antiviral mechanism in plants.

show abstract

Functions and regulation of the APOBEC family of proteins

Cited by 187 publications

References 147 publications

Transgenerational epigenetic effects of theApobec1cytidine deaminase deficiency on testicular germ cell tumor susceptibility and embryonic viability

Transgenerational epigenetic effects of theApobec1cytidine deaminase deficiency on testicular germ cell tumor susceptibility and embryonic viability

Transient overexpression of exogenous APOBEC3A causes C-to-U RNA editing of thousands of genes

A putative antiviral role of plant cytidine deaminases

Contact Info

Product

Resources

About