NCOA3 (nuclear receptor coactivator 3)

Review on NCOA3 (nuclear receptor coactivator 3), with data on DNA, on the protein encoded, and where the gene is implicated

Site Visit to New Jersey — State and County Experiences with Welfare Reform and Access to Health Care

This site visit was the second in a series to examine what is occurring at the state and local level with respect to welfare reform, Medicaid, public health, and safety net and other supportive services. During this visit, policymaker discovered how state officials, directors, and front-line staff at urban and suburban county welfare offices are working with clients to move them off the welfare rolls into jobs and providing the support services necessary for job retention; heard from clients about how programmatic changes are affecting them and their families; learned how the role of safety net health care and temporary housing providers is being affected by the reforms; and heard the perspective of advocates for and providers of services about how the reforms are affecting the economic status of the low-income population

Site Visit to Utah and Nevada — Essential Community Health Services on the Frontier

From the opening dinner to the closing summary, this site visit explored the delivery and financing of essential community services for vulnerable populations in the frontier West. A sequel to the Forum\u27s March 30-31, 1998, urban-centered site visit to Philadelphia, Providing Community-Based Primary Care: Nursing Centers, CHCs, and Other Initiatives, the visit spanned 493 miles. It included overview presentations, bus briefings, facility tours, telehealth demonstrations, panel discussions, and wrap-up reviews. Topics included the Utah health marketplace, the demands of emergency preparedness, the development of a patchwork of services along a continuum ranging from preventive care to tertiary referrals and follow-up, and various models of care (the nursing center, hospital or health system, community health center, migrant health service center, rural health clinic, and other examples). The visit also focused on special topics: private-public partnerships developed by a large health system to address safety- net issues, targeted services for Native Americans and for farm workers, and health workforce concerns

The AIB1 glutamine repeat polymorphism is not associated with risk of breast cancer before age 40 years in Australian women

INTRODUCTION: AIB1, located at 20q12, is a member of the steroid hormone coactivator family. It contains a glutamine repeat (CAG/CAA) polymorphism at its carboxyl-terminal region that may alter the transcriptional activation of the receptor and affect susceptibility to breast cancer through altered sensitivity to hormones. METHODS: We evaluated this repeat polymorphism in the context of early-onset disease by conducting a case-control study of 432 Australian women diagnosed with breast cancer before the age of 40 years and 393 population-based control individuals who were frequency matched for age. Genotyping was performed using a scanning laser fluorescence imager. RESULTS: There were no differences in genotype frequencies between cases and control individuals, or between cases categorized by family history or by BRCA1 and BRCA2 germline mutation status. There was no evidence that the presence of one or two alleles of 26 glutamine repeats or fewer was associated with breast cancer (odds ratio = 1.03, 95% confidence interval = 0.73–1.44), or that women with alleles greater than 29 repeats were at increased risk of breast cancer. Exclusion of women who carried a BRCA1 or BRCA2 mutation (24 cases) and non-Caucasian women (44 cases) did not alter the risk estimates or inferences. We present raw data, including that on mutation carriers, to allow pooling with other studies. CONCLUSION: There was no evidence that risk of breast cancer depends on AIB1 CAG/CAA polymorphism status, even if affected women carry a mutation in BRCA1 or BRCA2

Sequentiality and processivity of nuclear receptor coregulators in regulation of target gene expression

A series of data has accumulated over the past five years that raises questions about our current understanding of the transcriptional process and its regulation. Following the discovery of coactivators for nuclear receptors (NRs), a large number of these molecules have been reported in the literature. This perspective will summarize some opinions on the significance of this large number of factors

Photoperiodic regulation of androgen receptor and steroid receptor coactivator-1 in Siberian hamster brain

www.elsevier.com/locate/molbrainres Seasonal changes in the neuroendocrine actions of gonadal steroid hormones are triggered by fluctuations in daylength. The mechanisms responsible for photoperiodic influences upon the feedback and behavioral effects of testosterone in Siberian hamsters are poorly understood. We hypothesized that daylength regulates the expression of androgen receptor (AR) and/or steroid receptor coactivator-1 (SRC-1) in specific forebrain regions. Hamsters were castrated and implanted with either oil-filled capsules or low doses of testosterone; half of the animals remained in 16L/8D and the rest were kept in 10L/14D for the ensuing 70 days. The number of AR-immunoreactive (AR-ir) cells was regulated by testosterone in medial amygdala and caudal arcuate, and by photoperiod in the medial preoptic nucleus and the posterodorsal medial amygdala. A significant interaction between photoperiod and androgen treatment was found in medial preoptic nucleus and posterodorsal medial amygdala. The molecular weight and distribution of SRC-1 were similar to reports in other rodent species, and short days reduced the number of SRC-1-ir cells in posteromedial bed nucleus of the stria terminalis (BNST) and posterodorsal medial amygdala. A significant interaction between androgen treatment and daylength in regulation of SRC-1-ir was found in anterior medial amygdala. The present results indicate that daylength-induced fluctuations in SRC-1 and AR expression may contribute to seasonally changing effects of testosterone

Genetic Alterations in Intrahepatic Cholangiocarcinoma as revealed by Degenerate Oligonucleotide Primed PCR-Comparative Genomic Hybridization

Intrahepatic cholangiocarcinoma (ICC), a malignant neoplasm of the biliary epithelium, is usually fatal because of difficulty in early diagnosis and lack of availability of effective therapy. The genetic mechanisms involved in the development of ICC are not well understood and only a few cytogenetic studies of ICC have been published. Recently, technique of degenerate oligonucleotide primed (DOP)-PCR comparative genomic hybridization (CGH) permits genetic imbalances screening of the entire genome using only small amounts of tumor DNA. In this study chromosomal aberrations in 33 Korean ICC were investigated by DOP-PCR CGH. The common sites of copy number increases were 20q (67%), 17 (61%), 11q11-q13 (42%), 8p12-qter (39%), 18p (39%), 15q22-qter (36%), 16p (36%), 6p21 (30%), 3q25-qter (27%), 1q41-qter (24%), and 5p14-q11.2 (24%). DNA amplification was identified in 16 carcinomas (48%). The frequent sites of amplification were 20q, 17p, 17q23-qter, and 7p. The most frequent sites of copy number decreases were 1p32-pter (21%) and 4q (21%). The recurrent chromosomal aberrations identified in this study provide candidate regions involved in the tumorigenesis and progression of ICC

p160/SRC/NCoA coactivators form complexes via specific interaction of their PAS-B domain with the CID/AD1 domain

Transcriptional activation involves the ordered recruitment of coactivators via direct interactions between distinct binding domains and recognition motifs. The p160/SRC/NCoA coactivator family comprises three members (NCoA-1, -2 and -3), which are organized in multiprotein coactivator complexes. We had identified the PAS-B domain of NCoA-1 as an LXXLL motif binding domain. Here we show that NCoA family members are able to interact with other full-length NCoA proteins via their PAS-B domain and they specifically interact with the CBP-interaction domain (CID/AD1) of NCoA-1. Peptide competition, binding experiments and mutagenesis of LXXLL motifs point at distinct binding motif specificities of the NCoA PAS-B domains. NMR studies of different NCoA-1-PAS-B/LXXLL peptide complexes revealed similar although not identical binding sites for the CID/AD1 and STAT6 transactivation domain LXXLL motifs. In mechanistic studies, we found that overexpression of the PAS-B domain is able to disturb the binding of NCoA-1 to CBP in cells and that a CID/AD1 peptide competes with STAT6 for NCoA-1 in vitro. Moreover, the expression of an endogenous androgen receptor target gene is affected by the overexpression of the NCoA-1 or NCoA-3 PAS-B domains. Our study discloses a new, complementary mechanism for the current model of coactivator recruitment to target gene promoters

Homeostatic levels of SRC-2 and SRC-3 promote early human adipogenesis

Individual or joint knockdown of the transcriptional coactivators SRC-2 and SRC-3 inhibits lipid accumulation in adipocytes by decreasing PPARγ activity