The reflux-induced damage may lead to Barrett��s metaplasia, in which normal epithelium is XL-184 replaced by Barrett��s intestinal type epithelium. In some patients, this precancerous lesion may progress to esophageal dysplasia and adenocarcinoma, although little is currently known about specific mechanisms causing tumorigenic transformation of BE epithelium. p53 is an important regulator of DNA damage response and a key tumor suppressor. Its inactivation predisposes Barrett��s epithelial cells to the genomic instability and facilitates progression to cancer. p53 is also the founding member of a family of proteins, which includes two additional members, p63 and p73. These proteins have significant functional and structural similarities to p53, although certain specific differences exist in their regulation. Previous studies have found that p63 is downregulated following exposure to bile acids/acid, while p73 is induced and plays an important role in the regulation of DNA damage repair in esophageal cells. However, function of p73 is isoform-specific. The TP73 gene encapsulates ����two-in-one���� activities. N-terminally truncated p73 isoform, DNp73a, which lacks the transactivation domain, functions as a dominant-negative and oncogenic protein. It interacts with p53 and p73 proteins and inhibits their transcriptional and pro-apoptotic activities. When expressed, DNp73 exacerbates DNA damage induced by BA/A, immortalizes murine cells and induces their anchorage-independent growth. It also cooperates with other cellular oncogenes in cellular transformation and tumor development in mice. DNp73 is frequently over-expressed in human tumors including EA, and its level significantly correlates with poor patient survival in a number of human malignancies. However, regulation of the DNp73 protein remains largely unknown. Here we investigated the regulation of the DNp73 protein in conditions of gastroesophageal reflux. Transcriptional regulatory mechanisms specifying AB1010 neuronal subtype differentiation and gene expression remain enigmatic for most neurons in the central nervous system. The striatum, a component of the basal ganglia, is involved in motor coordination, emotion and cognition, and transcriptional regulation or dysregulation in its neurons is a feature of many prevalent neuropsychiatric diseases and their treatments. GABAergic, medium-sized spiny neurons are the striatal output neurons and comprise 90�C95% of its total neurons. Dopamine and cyclic AMP-regulated phosphoprotein, 32 kDa, encoded by the ppp1r1b gene, is expressed in 98% of the MSNs and modulates their response to dopamine and other first messengers. Although DARPP-32 is in fact expressed at a lower level throughout the forebrain, it is the most commonly used marker of the mature, post-mitotic, post-migrational MSN. Brain-derived neurotrophic factor is a major regulator of MSN phenotype during development and in the adult, and multiple molecular mechanisms via which it regulates ppp1r1b transcription have been well characterized. Many factors that contribute to neuronal differentiation and plasticity, including BDNF, lead to alterations of chromatin structure via core histone modifications, and inhibition of histone deacetylase activity promotes this process. In most cases, histone acetyltransferases acetylate lysine residues on the amino terminal tails of core histones, thereby relaxing chromatin structure and allowing for transcriptional activation. HDACs promote chromatin condensation by removing acetyl groups and therefore usually act as transcriptional repressors. HDAC inhibitors increase the association of acetylated histones with chromatin, thereby again relaxing chromatin condensation.