Редактирование: DDB2

DNA damage-binding protein 2 (DDB p48 subunit) (DDBb) (Damage-specific DNA-binding protein 2) (UV-damaged DNA-binding protein 2) (UV-DDB 2)

==Publications==

{{medline-entry
|title=Tumor regression by phenethyl isothiocyanate involves [[DDB2]].
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23114715
|abstract=Phenethyl isothiocyanate (PEITC) is a promising cancer chemopreventive agent commonly found in edible cruciferous vegetables. It has been implicated also for therapy, and is in clinical trial for lung cancer. Here, we provide evidence that the tumor suppressive effect of PEITC is related to its ability to induce expression of damaged DNA binding protein 2 ([[DDB2]]), a DNA repair protein involved also in apoptosis and premature senescence. [[DDB2]] expression is attenuated in a wide variety of cancers including the aggressive colon cancers. We show that, in colon cancer cells, reactive oxygen species, which are induced by PEITC, augment expression of [[DDB2]] through the p38MAPK/JNK pathway, independently of p53. PEITC-induced expression of [[DDB2]] is critical for inhibition of tumor progression by PEITC. Tumors derived from [[DDB2]]-deficient colon cancer cells are refractory to PEITC-treatments, resulting from deficiencies in apoptosis and senescence. The [[DDB2]]-proficient tumors, on the other hand, respond effectively to PEITC. The results show that PEITC can be used to induce expression of [[DDB2]], and that expression of [[DDB2]] is critical for effective response of tumors to PEITC.
|mesh-terms=* Animals
* Anticarcinogenic Agents
* Apoptosis
* Cell Line, Tumor
* DNA-Binding Proteins
* Disease Models, Animal
* Gene Expression Regulation, Neoplastic
* Humans
* Isothiocyanates
* Male
* Mice
* Neoplasms
* Reactive Oxygen Species
* Xenograft Model Antitumor Assays
|keywords=* DDB2
* PEITC
* ROS
* apoptosis
* colon cancer
* drug resistance
* senescence
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3571992
}}
{{medline-entry
|title=Damaged DNA binding protein 2 in reactive oxygen species (ROS) regulation and premature senescence.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23109835
|abstract=Premature senescence induced by DNA damage or oncogene is a critical mechanism of tumor suppression. Reactive oxygen species (ROS) have been implicated in the induction of premature senescence response. Several pathological disorders such as cancer, aging and age related neurological abnormalities have been linked to ROS deregulation. Here, we discuss how Damaged DNA binding Protein-2 ([[DDB2]]), a nucleotide excision repair protein, plays an important role in ROS regulation by epigenetically repressing the antioxidant genes MnSOD and Catalase. We further revisit a model in which [[DDB2]] plays an instrumental role in DNA damage induced ROS accumulation, ROS induced premature senescence and inhibition of skin tumorigenesis.
|mesh-terms=* Aging, Premature
* Animals
* Apoptosis
* Ataxia Telangiectasia Mutated Proteins
* Catalase
* Cell Transformation, Neoplastic
* Cellular Senescence
* Cullin Proteins
* DNA Damage
* DNA Repair
* DNA-Binding Proteins
* Humans
* Mice
* Reactive Oxygen Species
* Signal Transduction
* Skin Neoplasms
* Superoxide Dismutase
* Xeroderma Pigmentosum
|keywords=* DDB2
* NER
* apoptosis
* reactive oxygen species
* senescence
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3472727
}}
{{medline-entry
|title=Nucleotide excision DNA repair is associated with age-related vascular dysfunction.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/22705887
|abstract=Vascular dysfunction in atherosclerosis and diabetes mellitus, as observed in the aging population of developed societies, is associated with vascular DNA damage and cell senescence. We hypothesized that cumulative DNA damage during aging contributes to vascular dysfunction. In mice with genomic instability resulting from the defective nucleotide excision repair genes [[ERCC1]] and XPD (Ercc1(d/-) and Xpd(TTD) mice), we explored age-dependent vascular function compared with that in wild-type mice. Ercc1(d/-) mice showed increased vascular cell senescence, accelerated development of vasodilator dysfunction, increased vascular stiffness, and elevated blood pressure at a very young age. The vasodilator dysfunction was due to decreased endothelial nitric oxide synthase levels and impaired smooth muscle cell function, which involved phosphodiesterase activity. Similar to Ercc1(d/-) mice, age-related endothelium-dependent vasodilator dysfunction in Xpd(TTD) animals was increased. To investigate the implications for human vascular disease, we explored associations between single-nucleotide polymorphisms of selected nucleotide excision repair genes and arterial stiffness within the AortaGen Consortium and found a significant association of a single-nucleotide polymorphism (rs2029298) in the putative promoter region of [[DDB2]] gene with carotid-femoral pulse wave velocity. Mice with genomic instability recapitulate age-dependent vascular dysfunction as observed in animal models and in humans but with an accelerated progression compared with wild-type mice. In addition, we found associations between variations in human DNA repair genes and markers for vascular stiffness, which is associated with aging. Our study supports the concept that genomic instability contributes importantly to the development of cardiovascular disease.
|mesh-terms=* Aging
* Animals
* Blood Pressure
* Carotid Arteries
* Cells, Cultured
* Cellular Senescence
* DNA Repair
* DNA-Binding Proteins
* Endonucleases
* Endothelium, Vascular
* Femoral Artery
* Genomic Instability
* Humans
* Mice
* Mice, Inbred C57BL
* Mice, Mutant Strains
* Models, Animal
* Polymorphism, Single Nucleotide
* Vascular Stiffness
* Xeroderma Pigmentosum Group D Protein

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3430727
}}