Biomaterial Database

The Cytidine Deaminase APOBEC3 Family Is Subject to Transcriptional Regulation by p53. 2017

Daniel Menendez, and Thuy-Ai Nguyen, and Joyce Snipe, and Michael A Resnick

Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina. menendez@niehs.nih.gov.

The APOBEC3 (A3) family of proteins are DNA cytidine deaminases that act as sentinels in the innate immune response against retroviral infections and are responsive to IFN. Recently, a few A3 genes were identified as potent enzymatic sources of mutations in several human cancers. Using human cancer cells and lymphocytes, we show that under stress conditions and immune challenges, all A3 genes are direct transcriptional targets of the tumor suppressor p53. Although the expression of most A3 genes (including A3C and A3H) was stimulated by the activation of p53, treatment with the DNA-damaging agent doxorubicin or the p53 stabilizer Nutlin led to repression of the A3B gene. Furthermore, p53 could enhance IFN type-I induction of A3 genes. Interestingly, overexpression of a group of tumor-associated p53 mutants in TP53-null cancer cells promoted A3B expression. These findings establish that the "guardian of the genome" role ascribed to p53 also extends to a unique component of the immune system, the A3 genes, thereby integrating human immune and chromosomal stress responses into an A3/p53 immune axis.Implications: Activated p53 can integrate chromosomal stresses and immune responses through its influence on expression of APOBEC3 genes, which are key components of the innate immune system that also influence genomic stability. Mol Cancer Res; 15(6); 735-44. ©2017 AACR.

UI	MeSH Term	Description	Entries
D007370	Interferon Type I	Interferon secreted by leukocytes, fibroblasts, or lymphoblasts in response to viruses or interferon inducers other than mitogens, antigens, or allo-antigens. They include alpha- and beta-interferons (INTERFERON-ALPHA and INTERFERON-BETA).	Interferons Type I,Type I Interferon,Type I Interferons,Interferon, Type I,Interferons, Type I
D009154	Mutation	Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.	Mutations
D009369	Neoplasms	New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.	Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
D003564	Cytidine Deaminase	An enzyme that catalyzes the deamination of cytidine, forming uridine. EC 3.5.4.5.	Cytidine Aminohydrolase,Aminohydrolase, Cytidine,Deaminase, Cytidine
D005786	Gene Expression Regulation	Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.	Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000071478	APOBEC Deaminases	A family of conserved cytidine deaminases that catalyze the DEAMINATION of CYTIDINE to URIDINE. They are characterized by N and C-terminal zinc-dependent catalytic domains and have important functions in RNA EDITING; EPIGENTIC PROCESSES; and the INNATE IMMUNE RESPONSE against viruses.	AID-APOBEC Deaminases,APOBEC Enzymes,APOBEC Family Proteins,Apolipoprotein B mRNA Editing Enzyme, Catalytic Polypeptides,AID APOBEC Deaminases,Deaminases, AID-APOBEC,Deaminases, APOBEC
D016159	Tumor Suppressor Protein p53	Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.	p53 Tumor Suppressor Protein,Cellular Tumor Antigen p53,Oncoprotein p53,TP53 Protein,TRP53 Protein,p53 Antigen,pp53 Phosphoprotein,Phosphoprotein, pp53
D043525	Cytosine Deaminase	An enzyme which catalyzes the deamination of CYTOSINE resulting in the formation of URACIL. It can also act on 5-methylcytosine to form THYMIDINE.	Cytosine Aminohydrolase,Aminohydrolase, Cytosine,Deaminase, Cytosine
D045744	Cell Line, Tumor	A cell line derived from cultured tumor cells.	Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines